Methods of inhibiting cell proliferation using indeno [1,2-c]pyrazol-4-ones

ABSTRACT

The present invention relates to the synthesis of a new class of indeno[1,2-c]pyrazol-4-ones of formula (I):that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk1-7 and their regulatory subunits know as cyclins A-G. This invention also provides a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof. Alternatively, one can treat cancer or other proliferative diseases by administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

This application is a continuation of U.S. Ser. No. 09/295,078, filed Apr. 20, 1999 now abandoned which claims benefit 60/082,476 filed Apr. 21, 1998.

FIELD OF THE INVENTION

This invention relates generally to novel 5-substituted-indeno[1,2-c]pyrazol-4-ones which are useful as cyclin dependent kinase (cdk) inhibitors, pharmaceutical compositions comprising the same, methods for using the same for treating proliferative diseases, and intermediates and processes for making the same.

BACKGROUND OF THE INVENTION

One of the most important and fundamental processes in biology is the division of cells mediated by the cell cycle. This process ensures the controlled production of subsequent generations of cells with defined biological function. It is a highly regulated phenomenon and responds to a diverse set of cellular signals both within the cell and from external sources. A complex network of tumor promoting and suppressing gene products are key components of this cellular signaling process. Over expression of the tumor promoting components or the subsequent loss of the tumor suppressing products will lead to unregulated cellular proliferation and the generation of tumors (Pardee, Science 246:603-608, 1989).

Cyclin dependent kinases (cdks) play a key role in regulating the cell cycle machinery. These complexes consist of two components: a catalytic subunit (the kinase) and a regulatory subunit (the cyclin). To date, six kinase subunits (cdk 1-7) have been identified along with several regulatory subunits (cyclins A-H). Each kinase associates with a specific regulatory partner and together make up the active catalytic moiety. Each transition of the cell cycle is regulated by a particular cdk complex: G1/S by cdk2/cyclin E, cdk4/cyclin D1 and cdk6/cyclinD2; S/G2 by cdk2/cyclin A and cdk1/cyclin A; G2/M by cdk1/B. The coordinated activity of these kinases guides the individual cells through the replication process and ensures the vitality of each subsequent generation (Sherr, Cell 73:1059-1065, 1993; Draetta, Trends Biochem. Sci. 15:378-382, 1990)

An increasing body of evidence has shown a link between tumor development and cdk related malfunctions. Over expression of the cyclin regulatory proteins and subsequent kinase hyperactivity have been linked to several types of cancers (Jiang, Proc. Natl. Acad. Sci. USA 90:9026-9030, 1993; Wang, Nature 343:555-557, 1990). More recently, endogenous, highly specific protein inhibitors of cdks were found to have a major affect on cellular proliferation (Kamb et al, Science 264:436-440, 1994; Beach, Nature 336:701-704, 1993). These inhibitors include p16^(INK4) (an inhibitor of cdk4/D1), p21^(CIP1) (a general cdk inhibitor), and p27^(KIP1) (a specific cdk2/E inhibitor). A recent crystal structure of p27 bound to cdk2/A revealed how these proteins effectively inhibit the kinase activity through multiple interactions with the cdk complex (Pavletich, Nature 382:325-331, 1996). These proteins help to regulate the cell cycle through specific interactions with their corresponding cdk complexes. Cells deficient in these inhibitors are prone to unregulated growth and tumor formation.

This body of evidence has led to an intense search for small molecule inhibitors of the cdk family as an approach to cancer chemotherapy. There are no known examples of molecules related to the current invention which describe 5-substituted-indeno[1,2-c]pyrazoles as cdk inhibitors. There is one case describing indeno[1,2-c]pyrazoles having anticancer activity. There are two other examples which describe indeno[1,2-c]pyrazoles having unrelated utilities and structures.

A series of indeno[1,2-c]pyrazoles having anticancer activity are described in JP 60130521 and JP 62099361 with the following generic structure:

No substitution is claimed on the indenophenyl portion of the molecule and the molecules are not indicated to be cdk inhibitors. In addition, we discovered that substitution at the 5-position was critical for cdk inhibitory activity.

A series of indeno[1,2-c]pyrazoles having herbicidal activity are described in GB 2223946 with the following generic structure:

The above compounds differ from the presently claimed invention in X_(n) is defined as halo, alkyl, haloalkyl, and haloalkoxy; n=0-2. In addition, R₁ is defined as acyl and R₂ is defined as alkyl or cycloalkyl.

A series of 1-(6′-substituted-4′-methylquinol-2′-yl)-3-methylindeno[1,2-c]pyrazoles having CNS activity are described by Quraishi, Farmaco 44:753-8, 1989 with the following generic structure:

Compounds of this series are not considered to be part of the presently claimed invention.

SUMMARY OF THE INVENTION

The present invention describes a novel class of indeno[1,2-c]pyrazol-4-ones or pharmaceutically acceptable salt forms thereof that are potent inhibitors of the class of enzymes known as cyclin dependent kinases, which relate to the catalytic subunits cdk 1-7 and their regulatory subunits know as cyclins A-H.

It is another object of this invention to provide a novel method of treating cancer or other proliferative diseases by administering a therapeutically effective amount of one of these compounds or a pharmaceutically acceptable salt form thereof.

It is another object of this invention to provide a novel method of treating cancer or other proliferative diseases, which comprises administering a therapeutically effective combination of one of the compounds of the present invention and one or more other known anti-cancer or anti-proliferative agents.

These and other objectives have been achieved by the inventors' discovery that compounds of formula (I):

wherein R₁, R₂ and X are defined below or pharmaceutically acceptable salts thereof are cyclin dependent kinase inhibitors.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The invention pertains to novel cyclin dependent kinase inhibitors (cdks) and specifically, but not exclusively, as inhibitors of cdk/cyclin complexes. The inhibitors of this invention are indeno[1,2-c]pyrazol-4-one analogs. Certain analogs were selective for their activity against cdks and their cyclin bound complexes and were less active against other known serine/threonine kinases such as Protein Kinase A (PKA) and Protein Kinase C (PKC). In addition, these inhibitors were less active against tyrosine kinases such as c-Abl.

As described herein, the inhibitors of this invention are capable of inhibiting the cell-cycle machinery and consequently would be useful in modulating cell-cycle progression, which would ultimately control cell growth and differentiation. Such compounds would be useful for treating subjects having disorders associated with excessive cell proliferation, such as the treatment of cancer, psoriasis, immunological disorders involving unwanted leukocyte proliferation, in the treatment of restinosis and other smooth muscle cell disorders, and the like.

The present invention, in a first embodiment, describes a novel compound of formula (I):

or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein:

X is selected from the group: O, S, and NR;

R is selected from the group: H, C₁₋₄ alkyl, and NR⁵R^(5a);

R¹ is selected from the group: H, C₁₋₁₀ alkyl substituted with 0-3 R^(C), C₂₋₁₀ alkenyl substituted with 0-3 R^(c), C₂₋₁₀ alkynyl substituted with 0-3 R^(c), —NHR⁴, C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R^(b);

R^(a) is independently at each occurrence selected from the group: halo, —CN , N₃, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), ═O, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, SO₂NR³R^(3a), SO₂R^(3b), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S;

alternatively, when two R^(a)'s are present on adjacent carbon atoms they combine to form —OCH₂O— or —OCH₂CH₂O—;

R^(b) is independently at each occurrence selected from the group: halo, —CN, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), and SO₂R^(3b);

R^(c) is independently at each occurrence selected from the group: halo, —CN, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR⁵NR⁵R^(5a), NR³C(O)OR³, NR³C(O)R³, ═O, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R³;

R² is selected from the group: H, C₁₋₁₀ alkyl substituted with 0-3 R^(c), C₂₋₁₀ alkenyl substituted with 0-3 R^(c), C₂₋₁₀ alkynyl substituted with 0-3 R^(c), —(CF₂)_(m)CF₃, C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R^(b);

R³ is selected from the group: H, halo, —CN, NO₂, C₁₋₄ haloalkyl, NR⁵R^(5a), NR⁵NR⁵R^(5a), NR⁵C(O)OR⁵, NR⁵C(O)R⁵, ═O, OR⁵, COR⁵, CO₂R⁵, CONR⁵R^(5a), NHC(O)NR⁵R^(5a), NHC(S)NR⁵R^(5a), SO₂NR⁵R^(5a), SO₂R^(5b), C₁₋₄ alkyl, phenyl, and benzyl;

R^(3a) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

alternatively, R³ and R^(3a), together with the nitrogen atom to which they are attached, form a heterocycle having 4-8 atoms in the ring containing an additional 0-1 N, S, or O atom and substituted with 0-3 R^(3c);

R^(3b) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

R^(3c) is independently at each occurrence selected from the group: halo, —CN , N₃, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3b), ═O, OR³, COR³, CO₂R³, CONR³R³ ^(b) , NHC(O)NR³R³ ^(b) , NHC(S)NR³R³ ^(b) , NR³C(O)OR³, NR³C(O)R³, SO₂NR³R³ ^(b) , SO₂R^(3b), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S;

R⁴ is independently at each occurrence selected from the group: H, —CN, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R³;

R⁵ is independently selected from the group: H, C₁₋₄ alkyl, phenyl and benzyl;

R^(5a) is independently selected from the group: H, C₁₋₄ alkyl, phenyl and benzyl;

R^(5b) is independently selected from the group: H, C₁₋₄ alkyl, phenyl and benzyl; and

m is selected from 0, 1, 2, and 3.

In a preferred embodiment, the present invention provides a novel compound of formula (I), wherein:

X is selected from the group: O, S, and NR;

R is selected from the group: H, C₁₋₄ alkyl, and NR⁵R^(5a);

R¹ is selected from the group: H, C₁₋₅ alkyl substituted with 0-3 R^(c), C₂₋₅ alkenyl substituted with 0-3 R^(c), C₂₋₅ alkynyl substituted with 0-3 R^(c), —NHR⁴, C₃₋₆ carbocycle substituted with 0-5 R^(a), and 3-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R^(b);

R^(a) is independently at each occurrence selected from the group: halo, —CN, N₃, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, ═O, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S;

alternatively, when two R^(a)'s are present on adjacent carbon atoms they combine to form —OCH₂O— or —OCH₂CH₂O—;

R^(b) is independently at each occurrence selected from the group: halo, —CN, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), and SO₂R^(3b);

R^(c) is independently at each occurrence selected from the group: halo, —CN, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, NR⁵NR⁵R^(5a), ═O, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R³;

R² is selected from the group: H, C₁₋₅ alkyl substituted with 0-3 R^(c), C₂₋₅ alkenyl substituted with 0-3 R^(c), C₂₋₅ alkynyl substituted with 0-3 R^(c), —(CF₂)_(m)CF₃, C₃₋₆ carbocycle substituted with 0-5 R^(a), and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R^(b);

R³ is selected from the group: H, halo, —CN, NO₂, C₁₋₄ haloalkyl, NR⁵R^(5a), NR⁵NR⁵R^(5a), NR⁵C(O)OR⁵, NR⁵C(O)R⁵, ═O, OR⁵, COR⁵, CO₂R⁵, CONR⁵R^(5a), NHC(O)NR⁵R^(5a), NHC(S)NR⁵R^(5a), SO₂NR⁵R^(5a), SO₂R^(5b), C₁₋₄ alkyl, phenyl, and benzyl;

R^(3a) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

alternatively, R³ and R^(3a), together with the nitrogen atom to which they are attached, form a heterocycle having 4-8 atoms in the ring containing an additional 0-1 N, S, or O atom and substituted with 0-3 R^(3c);

R^(3b) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

R^(3c) is independently at each occurrence selected from the group: halo, —CN , N₃, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3b), ═O, OR³, COR³, CO₂R³, CONR³R³ ^(b) , NHC(O)NR³R³ ^(b) , NHC(S)NR³R³ ^(b) , NR³C(O)OR³, NR³C(O)R³, SO₂NR³R³ ^(b) , SO₂R^(3b), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S;

R⁴ is independently at each occurrence selected from the group: H, —CN, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R³;

R⁵ is independently selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

R^(5a) is independently selected from the group: H, C₁₋₄ alkyl, phenyl and benzyl;

R^(5b) is independently selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl; and

m is selected from 0, 1, 2, and 3.

In a more preferred embodiment, the present invention provides a novel compound of formula (I), wherein:

X is selected from the group: O and S;

R¹ is selected from the group: H, C₁₋₅ alkyl substituted with 0-3 R^(c), C₂₋₅ alkenyl substituted with 0-3 R^(c), —NHR⁴, C₃₋₆ carbocycle substituted with 0-5 R^(a), and 3-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R^(b);

R^(a) is independently at each occurrence selected from the group: halo, —CN, N₃, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S;

alternatively, when two R^(a)'s are present on adjacent carbon atoms they combine to form —OCH₂O— or —OCH₂CH₂O—;

R^(b) is independently at each occurrence selected from the group: halo, —CN, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), SO₂NR³R^(3a), and SO₂R^(3b);

R^(c) is independently at each occurrence selected from the group: halo, —CN, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR⁵NR⁵R^(5a), NR³C(O)OR³, NR³C(O)R³, ═O, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R³;

R² is selected from the group: H, C₁₋₅ alkyl substituted with 0-3 R^(c), C₂₋₅ alkenyl substituted with 0-3 R^(c), —(CF₂)_(m)CF₃, C₃₋₆ carbocycle substituted with 0-5 R^(a), and 3-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R^(b);

R³ is selected from the group: H, halo, —CN, NO₂, C₁₋₄ haloalkyl, NR⁵R^(5a), NR⁵NR⁵R^(5a), NR⁵C(O)OR⁵, NR⁵C(O)R⁵, ═O, OR⁵, COR⁵, CO₂R⁵, CONR⁵R^(5a), NHC(O)NR⁵R^(5a), NHC(S)NR⁵R^(5a), SO₂NR⁵R^(5a), SO₂R^(5b), C₁₋₄ alkyl, phenyl, and benzyl;

R^(3a) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

alternatively, R³ and R^(3a), together with the nitrogen atom to which they are attached, form a heterocycle having 5-6 atoms in the ring containing an additional 0-1 N, S, or O atom and substituted with 0-3 R^(3c);

R^(3b) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

R^(3c) is independently at each occurrence selected from the group: halo, —CN , N₃, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3b), ═O, OR³, COR³, CO₂R³, CONR³R³ ^(b) , NHC(O)NR³R³ ^(b) , NHC(S)NR³R³ ^(b) , NR³C(O)OR³, NR³C(O)R³, SO₂NR³R³ ^(b) , SO₂R^(3b), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S;

R⁴ is independently at each occurrence selected from the group: H, —CN, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R³;

R⁵ is independently selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

R^(5a) is independently selected from the group: H, C₁₋₄ alkyl, phenyl and benzyl;

R^(5b) is independently selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl; and

m is selected from 0, 1, 2, and 3.

In a even more preferred embodiment, the present invention provides a novel compound of formula (I), wherein:

X is selected from the group: O and S;

R¹ is selected from the group: H, C₁₋₅ alkyl substituted with 0-2 R^(c), —NHR⁴, C₃₋₆ carbocycle substituted with 0-5 R^(a), and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R^(b);

R^(a) is independently at each occurrence selected from the group: halo, —CN, N₃, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S;

alternatively, when two R^(a)'s are present on adjacent carbon atoms they combine to form —OCH₂O— or —OCH₂CH₂O—;

R^(b) is independently at each occurrence selected from the group: halo, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), SO₂NR³R^(3a), and SO₂R^(3b);

R^(c) is independently at each occurrence selected from the group: halo, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR⁵NR⁵R^(5a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R³;

R² is selected from the group: C₁₋₅ alkyl substituted with 0-3 R^(c), —(CF₂)_(m)CF₃, C₃₋₆ carbocycle substituted with 0-5 R^(a), and 5-6 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-3 R^(b);

R³ is selected from the group: H, halo, —CN, NO₂, C₁₋₄ haloalkyl, NR⁵R^(5a), NR⁵NR⁵R^(5a), NR⁵C(O)OR⁵, NR⁵C(O)R⁵, ═O, OR⁵, COR⁵, CO₂R⁵, CONR⁵R^(5a), NHC(O)NR⁵R^(5a), NHC(S)NR⁵R^(5a), SO₂NR⁵R^(5a), SO₂R^(5b), C₁₋₄ alkyl, phenyl, and benzyl;

R^(3a) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

alternatively, R³ and R^(3a), together with the nitrogen atom to which they are attached, form a heterocycle having 5-6 atoms in the ring containing an additional 0-1 N, S, or O atom and substituted with 0-3 R^(3c);

R^(3b) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl;

R^(3c) is independently at each occurrence selected from the group: halo, —CN , N₃, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3b), ═O, OR³, COR³, CO₂R³, CONR³R³ ^(b) , NHC(O)NR³R³ ^(b) , NHC(S)NR³R³ ^(b) , NR³C(O)OR³, NR³C(O)R³, SO₂NR³R³ ^(b) , SO₂R³ ^(b) , and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S;

R⁴ is independently at each occurrence selected from the group: H, —CN, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R³;

R⁵ is independently selected from the group: H and C₁₋₄ alkyl;

R^(5a) is independently selected from the group: H, C₁₋₄ alkyl, phenyl and benzyl;

R^(5b) is independently selected from the group: H and C₁₋₄ alkyl; and

m is selected from 0, 1, 2, and 3.

In a most preferred embodiment, the compounds of formula (I) are selected from:

3-(4-methoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methylthiophenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methylsulfonylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-N,N-dimethylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(3-pyridyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(formamido)indeno[1,2-c]pyrazol-4-one;

3-(4-hydroxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(1-piperidinyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-morpholinyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-ethoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-butylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-ethylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-n-propylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((4-aminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-pyridyl)-5-(formamido)indeno[1,2-c]pyrazol-4-one;

3-(4-pyridyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((4-aminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((4-azidophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((4-methoxycarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((4-aminomethylcarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((4-dimethylaminomethylcarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((4-acetamidophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(pyrrolidinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(morpholinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(thiomorpholinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(ethylaminoacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(piperidinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(piperazinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(4-methylpiperazinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(4-(2-hydroxyethyl)piperazinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(N,N-dimethylaminoacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((2-hydroxyethyl)aminoacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(aminoacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((2-chlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((2,4-dichlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((3,4-dichlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((2-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-dimethoxyphenyl)-5-((3-thiophene)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((3,4-ethylenedioxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(3,4-dimethoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(2-methoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((2,5-dimethoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((3,4-dimethoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((4-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((3-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-((4-chlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(butylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(4-aminobenzylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(4-pyridylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(phenylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(cyclobutylamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(cyclopentylamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(propylamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(ethylamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(benzylamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(isopropylamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(cyclopropylamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(chloroacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-methoxyphenyl)-5-(4-pyridinylaminomethylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-N,N-dimethylaminophenyl)-5-(morpholinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-N,N-dimethylaminophenyl)-5-(dimethylaminoacetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(trifluoromethyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(dimethylamino)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(dimethylamino)phenyl)-5-((4-aminomethyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(dimethylamino)phenyl)-5-((4-hydroxy-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(4-morpholinyl)phenyl)-5-((4-morpholinyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(4-morpholinyl)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(4-morpholinyl)phenyl)-5-((4-hydroxy-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(4-morpholinyl)phenyl)-5-((4-aminomethyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(1-piperazinyl)phenyl)-5-((4-morpholinyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(1-piperazinyl)phenyl)-5-((dimethylamino)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(1-piperazinyl)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(1-piperazinyl)phenyl)-5-((4-aminomethyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one;

3-(4-(1-piperazinyl)phenyl)-5-((aminocarbonyl)amino)indeno[1,2-c]pyrazol-4-one;

3-(4-(1-piperazinyl)phenyl)-5-((hydrazinocarbonyl)amino)indeno[1,2-c]pyrazol-4-one;

3-(4-(1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one;

3-(4-(4-methyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one;

3-(4-(4-ethyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one;

3-(4-(4-isopropyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one;

3-(4-(4-t-butoxycarbonyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one;

3-(4-(dimethylamino)phenyl)-5-((((4-methyl-1-piperazinyl)amino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one;

3-(i-propyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(c-propyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(t-butyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(2-thienyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(3-methyl-2-thienyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one;

3-(ethyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(n-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(i-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(c-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(c-hexyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(3-methyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-methyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-ethylcarboxyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(1-methyl-3-pyrrolyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(2,5-dimethyl-3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(2-furanyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(i-propyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(c-propyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(c-hexyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-methoxy-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-methyl-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-ethylcarboxyl-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(3-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-chloro-3-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(2,5-dimethyl-3-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(2-furanyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(i-propyl)-5-(4-carbamoylpiperidinylacetamido)indeno[1,2-c]pyrazol-4 -one;

3-(c-hexyl)-5-(4-carbamoylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(ethyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(i-propyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(c-propyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(c-hexyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one;

3-(i-propyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-ethylcarboxyl-2-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-carboxyl-2-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(2,5-dimethyl-3-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(i-propyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(N-methylcarbamoyl-4-piperidinyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-methyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-chloro-3-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(2,5-dimethyl-3-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-ethylcarboxyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-carboxyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-benzylcarboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-(4-methylpiperazinyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-(2-(1-methylpyrrolidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-(N,N-dimethylamino)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-(2-(N,N-dimethylamino)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-(2-(pyrrolidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-(2-(morpholinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-morpholinylcarboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-(3-(pyrrolidonyl)propyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-(3-(imidazolyl)propyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-(2-(2-pyridyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

3-(5-((2-pyridyl)methyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one; and

3-(5-(2-(piperidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one;

or pharmaceutically acceptable salt form thereof.

Another embodiment of the present invention is a pharmaceutical composition comprising: a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of formula (I).

Another embodiment of the present invention is a method of treating cancer and proliferative diseases comprising: administering to a host in need of such treatment a therapeutically effective amount of a compound of formula (I), or a pharmaceutically effective salt form thereof.

DEFINITIONS

As used herein, the following terms and expressions have the indicated meanings. The compounds of the present invention may contain an asymmetrically substituted carbon atom, and may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. All chiral, diastereomeric, racemic forms and all geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomer form is specifically indicated.

The term “alkyl” is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, and s-pentyl. In addition, the term is intended to include both unsubstituted and substituted alkyl groups, the latter referring to alkyl moieties having one or more hydrogen substituents replaced by, but not limited to halogen, hydroxyl, carbonyl, alkoxy, ester, ether, cyano, phosphoryl, amino, imino, amido, sulfhydryl, alkythio, thioester, sulfonyl, nitro, heterocyclo, aryl or heteroaryl. It will also be understood by those skilled in the art that the substituted moieties themselves can be substituted as well when appropriate.

The terms “halo” or “halogen” as used herein refer to fluoro, chloro, bromo and iodo. The term “aryl” is intended to mean an aromatic moiety containing the specified number of carbon atoms, such as, but not limited to phenyl, indanyl or naphthyl. The terms “cycloalkyl” and “bicycloalkyl” are intended to mean any stable ring system, which may be saturated or partially unsaturated. Examples of such include, but are not limited to, cyclopropyl, cyclopentyl, cyclohexyl, norbornyl, bicyclo[2.2.2]nonane, adamantly, or tetrahydronaphthyl (tetralin).

As used herein, “carbocycle” or “carbocyclic residue” is intended to mean any stable 3- to 7-membered monocyclic or bicyclic or 7- to 13-membered bicyclic or tricyclic, any of which may be saturated, partially unsaturated, or aromatic. Examples of such carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, cyclooctyl,; [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane (decalin), [2.2.2]bicyclooctane, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, or tetrahydronaphthyl (tetralin).

As used herein, the term “heterocycle” or “heterocyclic system” is intended to mean a stable 5- to 7-membered monocyclic or bicyclic or 7- to 10-membered bicyclic heterocyclic ring which is saturated partially unsaturated or unsaturated (aromatic), and which consists of carbon atoms and from 1 to 4 heteroatoms independently selected from the group consisting of N, O and S and including any bicyclic group in which any of the above-defined heterocyclic rings is fused to a benzene ring. The nitrogen and sulfur heteroatoms may optionally be oxidized. The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom which results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. If specifically noted, a nitrogen in the heterocycle may optionally be quaternized. It is preferred that when the total number of S and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. It is preferred that the total number of S and O atoms in the heterocycle is not more than 1. As used herein, the term “aromatic heterocyclic system” is intended to mean a stable 5- to 7- membered monocyclic or bicyclic or 7- to 10-membered bicyclic heterocyclic aromatic ring which consists of carbon atoms and from 1 to 4 heterotams independently selected from the group consisting of N, O and S. It is preferred that the total number of S and O atoms in the aromatic heterocycle is not more than 1.

Examples of heterocycles include, but are not limited to, 1H-indazole, 2-pyrrolidonyl, 2H,6H-1,5,2-dithiazinyl,2H-pyrrolyl, 3H-indolyl, 4-piperidonyl, 4aH-carbazole, 4H-quinolizinyl, 6H-1,2,5-thiadiazinyl, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazalonyl, carbazolyl, 4aH-carbazolyl, b-carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, oxazolidinyl., oxazolyl, oxazolidinylperimidinyl, phenanthridinyl, phenanthrolinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, pteridinyl, piperidonyl, 4-piperidonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, carbolinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, xanthenyl. Preferred heterocycles include, but are not limited to, pyridinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, indolyl, benzimidazolyl, 1H-indazolyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, or isatinoyl. Also included are fused ring and spiro compounds containing, for example, the above heterocycles.

As used herein, “pharmaceutically acceptable salts” refer to derivatives of the disclosed compounds wherein the parent compound is modified by making acid or base salts thereof. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include the conventional non-toxic salts or the quaternary ammonium salts of the parent compound formed, for example, from non-toxic inorganic or organic acids. For example, such conventional non-toxic salts include those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, and the like.

The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, nonaqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 18th ed., Mack Publishing Company, Easton, Pa., 1990, p. 1445, the disclosure of which is hereby incorporated by reference.

The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication commensurate with a reasonable benefit/risk ratio.

“Prodrugs”, as the term is used herein, are intended to include any covalently bonded carriers which release an active parent drug of the present invention in vivo when such prodrug is administered to a mammalian vivo when such prodrug is administered to a mammalian subject. Since prodrugs are known to enhance numerous desirable qualities of pharmaceuticals (i.e., solubility, bioavailability, manufacturing, etc.) the compounds of the present invention may be delivered in prodrug form. Thus, the present invention is intended to cover prodrugs of the presently claimed compounds, methods of delivering the same, and compositions containing the same. Prodrugs of the present invention are prepared by modifying functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Prodrugs include compounds of the present invention wherein a hydroxy, amino, or sulfhydryl group is bonded to any group that, when the prodrug of the present invention is administered to a mammalian subject, it cleaves to form a free hydroxyl, free amino, or free sulfydryl group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate, and benzoate derivatives of alcohol and amine functional groups in the compounds of the present invention.

“Substituted” is intended to indicate that one or more hydrogens on the atom indicated in the expression using “substituted” is replaced with a selection from the indicated group(s), provided that the indicated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto (i.e., ═O) group, then 2 hydrogens on the atom are replaced.

As used herein, the term “anti cancer” or “anti-proliferative” agent includes, but is not limited to, altretamine, busulfan, chlorambucil, cyclophosphamide, ifosfamide, mechlorethamine, melphalan, thiotepa, cladribine, fluorouracil, floxuridine, gemcitabine, thioguanine, pentostatin, methotrexate, 6-mercaptopurine, cytarabine, carmustine, lomustine, streptozotocin, carboplatin, cisplatin, oxaliplatin, iproplatin, tetraplatin, lobaplatin, JM216, JM335, fludarabine, aminoglutethimide, flutamide, goserelin, leuprolide, diethylstilbestrol, prednisone, bleomycin, dactinomycin, daunorubicin, doxirubicin, idarubicin, mitoxantrone, losoxantrone, mitomycin-c, plicamycin, paclitaxel, docetaxel, topotecan, irinotecan, 9-amino camptothecan, 9-nitro camptothecan, GS-211, etoposide, teniposide, vinblastine, vincristine, vinorelbine, procarbazine, asparaginase, pegaspargase, octreotide, estramustine, hydroxyurea.

SYNTHESIS

The compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or variations thereon as appreciated by those skilled in the art. Preferred methods include, but are not limited to, those methods described below. Each of the references cited below are hereby incorporated herein by reference.

An approach to preparing indeno[1,2-c]pyrazol-4-ones is presented in Scheme 1 and can be used to prepare compounds of the present invention. The nitro group of dimethyl 3-nitrophthalate was reduced to the amine using catalytic hydrogenation. The aniline was acylated using acetic anhydride and pyridine as a base. A mixture of the resulting acetamide 2 and an acetophenone were treated with a strong base in an appropriate solvent at elevated temperature to give the desired triketone 3. Additional means of preparing triketones are known to one skilled in the art as described in Kilgore et al, Industrial and Engineering Chemistry 34:494-497, 1946, the contents of which are hereby incorporated herein by reference. The triketone was treated with hydrazine at elevated temperature in an appropriate solvent to give the indeno[1,2-c]pyrazol-4-one ring system. Additional means of preparing indeno[1,2-c]pyrazol-4-ones are known to one skilled in the art as described in Lemke et al., J. Heterocyclic Chem. 19:1335-1340, 1982; Mosher and Soeder, J. Heterocyclic Chem. 8:855-59, 1971; Hrnciar and Svanygova Collect. Czech. Chem. Commun. 59:2734-40, 1994 the contents of which are hereby incorporated herein by reference. The amide was deacylated by heating with a strong acid in an appropriate solvent to give aniline 4. This aniline was acylated under standard conditions using an acid chloride in an appropriate solvent to give the desired product 5.

An alternative method for making compounds of the present invention is shown in Scheme 2. The intermediate triketone 3 can be deacylated with strong acid and reacylated with an appropriate acid chloride using methods known to those skilled in the art. Subsequently, triketone 6 can the be converted to the indeno[1,2-c]pyrazol-4-one ring system using the same conditions described previously in Scheme 1.

Another method for preparing the triketones 6 of Scheme 2 employs the condensation of a 1,3-diketone 6a with 3-nitrophthalic anhydride as described in Rotberg and Oshkaya, Zh. Organ. Khim. 8:84-87, 1972; Zh. Organ. Khim. 9:2548-2550, 1973, the contents of which are hereby incorporated herein by reference. The 1,3-diketones, when not commercially available can be readily prepared by one skilled in the art by the acetylation or trifluoroacetylation of the requisite methyl ketone, R¹COCH₃. Reduction of the nitro derivative 6b to the aniline 6c can be accomplished in a variety of ways including catalyic hydrogenation, treatment with zinc or iron under acidic conditions, or treatment with other reducing agents such as sodium dithionite or stannous chloride. Subsequently the aniline 6c can be converted to the indeno[1,2-c]pyrazol-4-ones of this invention by acylation followed by treatment with hydrazine as described previously in Scheme 2.

Another method for making the indeno[l,2-c]pyrazol-4-one ring system is shown in Scheme 4. Dimethyl hydrazine was reacted with 3-acetylpyridine with no solvent to give the hydrazone 7. This was treated in a similar fashion as described in Scheme 1 to give the desired intermediate 8. Additional means of preparing similar intermediates are known to one skilled in the art as described in Rappoport, J. Org. Chem. 49:2948-2953, 1984, the contents of which are hereby incorporated herein by reference. This intermediate was carried through the sequence in a similar fashion as described in Scheme 1.

Other features of the invention will become apparent during the following descriptions of exemplary embodiments which are given for illustration of the invention and are not intended to be limiting thereof.

EXAMPLES

Abbreviations used in the Examples are defined as follows: “° C.” for degrees Celsius, “CIMS” for chemical ionization mass spectroscopy, “eq” for equivalent or equivalents, “g” for gram or grams, “h” for hour or hours, “mg” for milligram or milligrams, “mL” for milliliter or milliliters, “mmol” for millimolar, “M” for molar, “min” for minute or minutes, “p-TsOH” for para-toluenesulphonic acid, “DMF” for dimethylformamide, and “TFA” for trifluoroacetic acid.

Example I

Preparation of 3-(4-methoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 2 From Dimethyl 3-nitrophthalate

A solution of dimethyl 3-nitrophthalate (25 g, 105 mmol) in methanol (100 mL) was treated with 5% Pd/C (2.5 g) and hydrogenated on a Parr Shaker at 50 psi for 2 h. The solution was filtered (Celite), the filtrate collected and the solvent removed at reduced pressure. The residue was dissolved in acetic anhydride (20 mL) treated with pyridine (0.05 mL) and heated to 80° C. for 1 min. The reaction was cooled and stirred at 25° C. for 2 h. The solvent was removed at reduced pressure and the residue recrystallized from ethanol to give the product as a white solid (21 g, 79%). mp 104-105° C.; CIMS m/e calc'd for C₁₂H₁₄NO₅: 252.0872, found 252.0888; Analysis calc'd for C₁₂H₁₃NO₅: C, 57.37; H, 5.22; N, 5.58; found: C, 57.67; H, 5.29; N, 5.77.

Step 2. Synthesis of Triketone 11 From 2

A solution of 2 (1 g, 4.0 mmol) in dry DMF (2 mL) was treated with sodium hydride (0.15 g, 60% suspension in oil, 0.4 mmol) in one portion. After 1 h, 4-methoxyacetophenone (0.6 g, 4.0 mmol) was added in one portion and the reaction heated to 90° C. A second portion of sodium hydride (0.15 g, 60% suspension in oil, 0.4 mmol) was added and the exothermic reaction turns deep red. After 20 min, the reaction was cooled to 25° C., diluted with water (20 mL), extracted with EtOAc (10 mL) and the aqueous phase separated. The aqueous phase was acidified with 2 N HCl to pH 2 and the crude product collected. Recrystalization with ethanol gave the desired product as a yellow solid (0.4 g, 30%). mp 174-175° C.; CIMS m/e calc'd for C₁₉H₁₆NO₅: 338.1028, found 338.1022; Analysis calc'd for C₁₉H₁₅NO₅: C, 67.65; H, 4.48; N, 4.15; found: C, 67.87; H, 4.29; N, 3.99.

Step 3. Synthesis of 12 From 11

A solution of 11 (0.2 g, 0.6 mmol) in EtOH (5 mL) was treated with hydrazine hydrate (0.1 mL, 1.8 mmol) and p-TsOH (3 mg). The reaction was heated to reflux and stirred for 2 h. The reaction was cooled to 25° C. and the product collected as a yellow solid (0.1 g, 50%). mp 268° C.; CIMS m/e calc'd for C₁₉H₁₆N₃O₃: 334.1192, found: 334.1168; Analysis calc'd for C₁₉H₁₅N₃O₃: C, 68.46; H, 4.54; N, 12.61; found: C, 68.81; H, 4.39; N, 12.45.

Example II

Preparation of 3-(4-methoxyphenyl)-5-(chloroacetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 13 From 12

A suspension of 12 (1.0 g, 3.0 mmol) in MeOH (10 mL) was treated with conc. HCl (1 mL) and heated to reflux. After 2 h, the reaction was cooled and the product was collected as a greenish solid (0.7 g, 81%). mp 273° C.; CIMS m/e calc'd for C₁₇H₁₄N₃O₂: 292.1086, found: 292.1080; Analysis calc'd for C₁₇H₁₃N₃O₂: C, 69.85; H, 4.83; N, 14.37; found: C, 69.99; H, 4.59; N, 14.44.

Step 2. Synthesis of 14 From 13

A suspension of 13 (20 mg, 0.07 mmol) in dioxane (2 mL) was treated with aqueous sat. NaHCO₃ (1 mL) and chloroacetyl chloride (30 mL, 0.21 mmol). The reaction was heated to 50° C. and stirred for 2 h. The reaction was cooled, poured into water (2 mL), extracted with EtOAc (10 mL), the organic layer separated, dried (MgSO₄) and the solvent removed at reduced pressure. The solid residue was recrystallized from EtOH to give the product as a yellow solid (9 mg, 35%). mp 274° C.; CIMS m/e calc'd for C₁₉H₁₅N₃O₃Cl: 368.0802, found: 368.0818.

Example III

Preparation of 3-(4-methoxyphenyl)-5-(cyclopropylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using cyclopropylacetyl chloride as the starting material. mp 289° C.; CIMS m/e calc'd for C₂₁H₁₈N₃O₃: 360.1348, found: 360.1330.

Example IV

Preparation of 3-(4-methoxyphenyl)-5-(isopropylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using isopropylacetyl chloride as the starting material. mp 288° C.; CIMS m/e calc'd for C₂₁H₂₀N₃O₃: 362.1505, found: 362.1535.

Example V

Preparation of 3-(4-methoxyphenyl)-5-(ethylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using propionyl chloride as the starting material. mp 287° C.; CIMS m/e calc'd for C_(2O)H₁₈N₃O₃: 348.1348, found: 348.1313.

Example VI

Preparation of 3-(4-methoxyphenyl)-5-(cyclopentylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using cyclopentylacetyl chloride as the starting material. mp 267° C.; CIMS m/e calc'd for C₂₃H₂₂N₃O₃: 388.1661, found: 388.1626.

Example VII

Preparation of 3-(4-methoxyphenyl)-5-(cyclobutylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using cyclobutylacetyl chloride as the starting material. mp 297° C.; CIMS m/e calc'd for C₂₂H₂₀N₃O₃: 374.1505, found: 374.1530.

Example VIII

Preparation of 3-(4-methoxyphenyl)-5-(phenylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using phenylacetyl chloride as the starting material. mp 280° C.; CIMS m/e calc'd for C₂₅H₂₀N₃O₃: 410.1505, found: 410.1533.

Example IX

Preparation of 3-(4-methoxyphenyl)-5-(butylamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using butyryl chloride as the starting material. mp 282° C.; CIMS m/e calc'd for C₂₁H₂₀N₃O₃: 362.1505, found: 362.1500.

Example X

Preparation of 3-(4-methoxyphenyl)-5-((4-chlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using 4-chlorophenylacetyl chloride as the starting material. mp 238° C.; CIMS m/e calc'd for C₂₅H₁₉N₃O₃Cl: 444.1115, found: 444.1110.

Example XI

Preparation of 3-(4-methoxyphenyl)-5-((3-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using 3-methoxyphenylacetyl chloride as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₆H₂₂N₃O₄: 440.1610, found: 440.1620.

Example XII

Preparation of 3-(4-methoxyphenyl)-5-((4-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using 4-methoxyphenylacetyl chloride as the starting material. mp 280° C.; CIMS m/e calc'd for C₂₆H₂₂N₃O₄: 440.1610, found: 440.1630.

Example XIII

Preparation of 3-(4-methoxyphenyl)-5-((3,4-dimethoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using 3,4-dimethoxyphenylacetyl chloride as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₇H₂₄N₃O₅: 470.1716, found: 470.1731.

Example XIV

Preparation of 3-(4-methoxyphenyl)-5-((2,5-dimethoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example II using 2,5-dimethoxyphenylacetyl chloride as the starting material. mp 226° C.; CIMS m/e calc'd for C₂₇H₂₄N₃O₅: 470.1716, found: 470.1739.

Example XV

Preparation of 3-(2-methoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 2-methoxyacetophenone as the starting material. mp 276° C.; CIMS m/e calc'd for C₁₉H₁₆N₃O₃: 334.1192, found: 334.1169.

Example XVI

Preparation of 3-(3,4-dimethoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 3,4-dimethoxyacetophenone as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₀H₁₈N₃O₄: 364.1297, found: 364.1288.

Example XVII

Preparation of 3-(4-methoxyphenyl)-5-((3,4-ethylenedioxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 15 From 11

A suspension of 11 (5 g, 14.8 mmol) in MeOH (50 mL) was treated with conc. HCl (3 mL) and heated to reflux. After stirring for 2 h, the reaction was cooled to 0° C. and the product collected as a yellow solid (4.2 g, 96%). mp 173° C.; CIMS m/e calc'd for C₁₇H₁₄NO₄: 296.0923, Found: 296.0901.

Step 2. Synthesis of 16 From 15

A suspension of 15 (20 mg, 0.07 mmol) in acetone (2 mL) was treated with NaHCO₃ (10 mg) and the acid chloride of (3,4-methylenedioxyphenyl)acetic acid (prepared by heating the acid in a benzene:thionyl chloride 4:1 mixture at 50° C. for 2 h, removing the volatile components at reduced pressure, and using the crude acid chloride without further purification). The reaction was heated to 50° C. and stirred for 2 h. The reaction was cooled, poured into water (4 mL), extracted with EtOAc (10 mL), dried (MgSO₄), filtered and concentrated. The crude triketone was suspended in EtOH (2 mL), treated with hydrazine hydrate (0.05 mL) and p-TsOH (1 mg) and heated to reflux for 2 h. The reaction was cooled to 0° C. and the product filtered to give a yellow solid (6.5 mg, 20%). mp 297° C.; CIMS m/e calc'd for C₂₆H₂₀N₃O₅: 454.1403, Found: 454.1398.

Example XVIII

Preparation of 3-(4-dimethoxyphenyl)-5-((3-thiophene)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using the acid chloride of 3-thiopheneacetic acid as the starting material. mp 293° C.; CIMS m/e calc'd for C₂₃H₁₈N₃O₃S: 416.1069, found: 416.1088.

Example XIX

Preparation of 3-(4-methoxyphenyl)-5-((2-methoxyphenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using the acid chloride of 2-methoxyphenylacetic acid as the starting material. mp 255° C.; CIMS m/e calc'd for C₂₆H₂₂N₃O₄: 440.1610, found: 440.1622.

Example XX

Preparation of 3-(4-methoxyphenyl)-5-((3,4-dichlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using the acid chloride of 3,4-dichlorophenylacetic acid as the starting material. mp 299° C.; CIMS m/e calc'd for C₂₅H₁₈N₃O₃Cl₂: 478.0725, found: 478.0744.

Example XXI

Preparation of 3-(4-methoxyphenyl)-5-((2,4-dichlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using the acid chloride of 2,4-dichlorophenylacetic acid as the starting material. mp 286° C.; CIMS m/e calc'd for C₂₅H₁₈N₃O₃Cl₂: 478.0725, found: 478.0734.

Example XXII

Preparation of 3-(4-methoxyphenyl)-5-((2-chlorophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XVII using the acid chloride of 2-chlorophenylacetic acid as the starting material. mp 300° C.; CIMS m/e calc'd for C₂₅H₁₉N₃O₃Cl: 444.1115, found: 444.1111.

Example XXIII

Preparation of 3-(4-methoxyphenyl)-5-(aminoacetamido)indeno[1,2-c]pyrazol-4-one

A suspension of 14 (15 mg, 0.04 mmol) in EtOH (1 mL) was treated with conc. NH₄OH (1 mL), placed in a sealed tube and heated to 80° C. for 3 h. The reaction was cooled and the solvent removed at reduced pressure. The residue was recrystallized from EtOH to give the product as a yellow solid (9 mg, 62%). mp >300° C.; CIMS m/e calc'd for C₂₀H₁₉N₄O₃: 363.1457, Found: 363.1431.

Example XXIV

Preparation of 3-(4-methoxyphenyl)-5-((2-hydroxyethyl)aminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using hydroxylamine as the starting material. mp 243° C.; CIMS m/e calc'd for C₂₁H₂₁N₄O₄: 393.1563, found: 393.1539.

Example XXV

Preparation of 3-(4-methoxyphenyl)-5-(N,N-dimethylaminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using dimethylamine as the starting material. mp 279° C.; CIMS m/e calc'd for C₂₁H₂₁N₄O₃: 377.1614, found: 377.1640.

Example XXVI

Preparation of 3-(4-methoxyphenyl)-5-(piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using piperazine as the starting material. mp 277° C.; CIMS m/e calc'd for C₂₃H₂₄N₅O₃: 418.1879, found: 418.1899.

Example XXVII

Preparation of 3-(4-methoxyphenyl)-5-(4-methylpiperazinylacetamido)indenol[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-methylpiperizine as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₄H₂₆N₅O₃: 432.2036, found: 432.2030.

Example XXVIII

Preparation of 3-(4-methoxyphenyl)-5-(4-(2-hydroxyethyl)piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-hydroxyethylpiperizine as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₅H₂₈N₅O₄: 462.2141, found: 462.2128.

Example XXIX

Preparation of 3-(4-methoxyphenyl)-5-(piperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using piperidine as the starting material. mp 291° C.; CIMS m/e calc'd for C₂₄H₂₅N₄O₃: 417.1927, found: 417.1955.

Example XXX

Preparation of 3-(4-methoxyphenyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-aminomethylpiperidine as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₅H₂₈N₅O₃: 446.2192, found: 446.2166.

Example XXXI

Preparation of 3-(4-methoxyphenyl)-5-(ethylaminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using ethylamine as the starting material. mp 250° C.; CIMS m/e calc'd for C₂₁H₂₁N₄O₃: 377.1614, found: 377.1644.

Example XXXII

Preparation of 3-(4-methoxyphenyl)-5-(thiomorpholinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using thiomorpholine as the starting material. mp 298° C.; CIMS m/e calc'd for C₂₃H₂₃N₄O₃S: 435.1491, found: 435.1477.

Example XXXIII

Preparation of 3-(4-methoxyphenyl)-5-(morpholinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using morpholine as the starting material. mp 295° C.; CIMS m/e calc'd for C₂₃H₂₃N₄O₄: 419.1719, found: 419.1744.

Example XXXIV

Preparation of 3-(4-methoxyphenyl)-5-(pyrrolidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using pyyrolidine as the starting material. mp 279° C.; CIMS m/e calc'd for C₂₃H₂₃N₄O₃: 403.1770, found: 403.1761.

Example XXXV

Preparation of 3-(4-methoxyphenyl)-5-(4-pyridinylaminomethylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-aminomethylpyridine as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₅H₂₂N₅O₃: 440.1723, found: 440.1762.

Example XXXVI

Preparation of 3-(4-methoxyphenyl)-5-((4-acetamidophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

A suspension of 18 (10 mg, 0.02 mmol) in dioxane (1 mL) was treated with aqueous sat. NaHCO₃ (0.5 mL) and acetyl chloride (0.01 mL) and heated at 50° C. for 1 h. The reaction was cooled, poured into water (5 mL), extracted with EtOAc (10 mL), the organic layer separated, dried (MgSO₄) and the solvent removed at reduced pressure. The residue was recrystallized from EtOH to give the product as a yellow solid (5.6 mg, 61%). mp 268° C.; CIMS m/e calc'd for C₂₇H₂₃N₄O₄: 467.1719, Found: 467.1730.

Example XXXVII

Preparation of 3-(4-methoxyphenyl)-5-((4-methoxycarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXXII using methylchloroformate as the starting material. mp 257° C.; CIMS m/e calc'd for C₂₇H₂₃N₄O₅: 483.1668, found: 483.1633.

Example XXXVIII

Preparation of 3-(4-methoxyphenyl)-5-((4-aminomethylcarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII and XXXII using chloroacetyl chloride and conc. NH₄OH as the starting materials. mp 228° C.; CIMS m/e calc'd for C₂₇H₂₄N₅O₄: 482.1828, found: 482.1844.

Example XXXIX

Preparation of 3-(4-methoxyphenyl)-5-((4-N,N-dimethylaminomethylcarbonylaminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII and XXXII using chloroacetyl chloride and dimethyl amine as the starting materials. mp>300° C.; CIMS m/e calc'd for C₂₉H₂₈N₅O₄: 510.2141, found: 510.2121.

Example XL

Preparation of 3-(4-methoxyphenyl)-5-((4-azidophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

A solution of example XXXVI (20 mg, 0.04 mmol) in DMF (2 mL) was treated with 5% palladium on carbon (5 mg) and hydrogentaed at atmospheric pressure using a hydrogen baloon. After 2 h, the solution was filtered (Celite), and the solvent removed at reduced pressure. The residue was recrystallized from EtOH to give the product as a yellow solid (15 mg, 78%). mp>300° C.; CIMS m/e calc'd for C₂₅H₁₉N₆O₃: 451.1519, found: 451.1544.

Example XLI

Preparation of 3-(4-methoxyphenyl)-5-((4-aminophenyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXVII using the acid chloride of 4-azidophenylacetic acid as the starting material. mp 283° C.; CIMS m/e calc'd for C₂₅H₂₁N₄O₃: 425.1614, found: 425.1643.

Example XLII

Preparation of 3-(4-methoxyphenyl)-5-(phenylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 20 From 15

A suspension of 15 (0.5 g, 1.7 mmol) in acetone (10 mL) was treated with NaHCO₃ (0.5 g) and phenyl chloroformate. The mixture was heated to 50° C. for 2 h. The reaction was cooled, poured into water (20 mL), extracted with EtOAc (40 mL), the organic layer separated, dried (MgSO₄) and the solvent removed at reduced pressure. The residue was suspended in EtOH (10 mL) and treated with hydrazine hydrate (0.16 mL, 5.1 mmol) and p-TsOH (10 mg). The mixture was heated to reflux and stirred for 3 h. The reaction was cooled to 0° C. and the product collected as a yellow solid (0.25 g, 36%). mp 195° C.; CIMS m/e calc'd for C₂₄H₁₈N₃O₄: 412.1297, Found: 412.1308.

Step 2. Synthesis of 21 From 20

A solution of 20 (20 mg, 0.05 mmol) in DMSO (2 mL) was treated with aniline (20 mL, mmol) and dimethylaminopyridine (1 mg). The mixture was heated to 80° C. for 2 h. The reaction was cooled, poured into water (4 mL), extracted with EtOAc (15 mL), the organic layer separated, dried (MgSO₄) and the solvent removed at reduced pressure. The residue was recrystallized from EtOH to give the product as a yellow solid (9 mg, 44%). mp>300° C.; CIMS m/e calc'd for C₂₄H₁₉N₄O₃: 411.1457, Found: 411.1432.

Example XLIII

Preparation of 3-(4-methoxyphenyl)-5-(butylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using butyl amine as the starting material. mp 252° C.; CIMS m/e calc'd for C₂₁H₂₁N₄O₃: 377.1614, found: 377.1633.

Example XLIV

Preparation of 3-(4-methoxyphenyl)-5-(4-aminobenzylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using 4-aminobenzyl amine as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₅H₂₂N₅O₃: 440.1723, found: 440.1700.

Example XLV

Preparation of 3-(4-methoxyphenyl)-5-(4-pyridylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using 4-aminomethylpyridine as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₄H₂₀N₅O₃: 426.1566, found: 426.1533.

Example XLVI

Preparation of 3-(4-hydroxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

A suspension of 12 (20 mg, 0.07 mmol) in CH₂Cl₂ (2 mL) was treated with excess BBr₃ (1.0 mL, 1.0 M in CH₂Cl₂) and stirred for 20 h. The reaction was slowly poured into aqueous sat. NaHCO₃ (5 mL), extracted with EtOAc (10 mL), dried (MgSO₄) and concentrated. The residue was recrystallized from EtOH to give the desired product as a yellow solid (7.5 mg, 33%). mp>300° C.; CIMS m/e calc'd for C₁₈H₁₄N₃O₃: 320.1035, Found: 320.1050.

Example XLVII

Preparation of 3-(4-methoxyphenyl)-5-(formamido)indeno[1,2-c]pyrazol-4-one

A suspension of 13 (20 mg, 0.06 mmol) in formic acid (2 mL) was heated to 100° C. for 2 h. The reaction mixture was cooled and the solvent removed at reduced pressure. The residue was recrystallized from EtOH to give the desired product as a yellow solid (12 mg, 63%). mp 280° C.; CIMS m/e calc'd for C₁₈H₁₄N₃O₃: 320.1035, Found: 320.1040.

Example XLVIII

Preparation of 3-(3-pyridyl)-5-(acetamido) indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 24 From 3-acetylpyridine

A solution of 3-acetylpyridine (1.0 g, 8.3 mmol) in benzene (3 mL) was treated with 1,1-dimethylhydrazine (0.62 mL, 8.3 mmol) and p-TsOH (5 mg). The mixture was heated to 85° C. and stirred for 3 h. The reaction was cooled and the solvent removed at reduced pressure. This crude hydrazone was treated with 1.0 M NaN(TMS)₂ in THF (16.6 mL, 16.6 mmol) at 25° C. over 5 min. After 30 min dimethyl 3-acetamidophthalate (2.1 g, 8.3 mmol) was added in one portion and the reaction heated to reflux. Stirring was continued for 6 h. The reaction was cooled and quenched by the slow addition of TFA. The solvent was removed at reduced pressure and the residue chromatographed (silica, 2.5-5% MeOH/CH₂Cl₂) to give the product as a yellow solid (0.35 g, 14%). mp 265° C.; CIMS m/e calc'd for C₁₇H₁₃N₂O₄: 309.0875, Found: 309.0888.

Step 2. Synthesis of 25 From 24.

A suspension of 24 (30 mg, 0.09 mmol) in EtOH (2 mL) was treated with hydrazine hydrate (0.05 mL) and p-TsOH (1 mg) and heated to reflux. After stirring for 2 h. the reaction was cooled and the product filtered to give a yellow solid (12 mg, 44%). mp>300° C.; CIMS m/e calc'd for C₁₇H₁₃N₄O₂: 305.1039, Found: 305.1048.

Example XLIX

Preparation of 3-(4-pyridyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLVIII using 4-acetylpyridine as the starting material. mp >300° C.; CIMS m/e calc'd for C₁₇H₁₃N₄O₂: 305.1039, found: 305.1046.

Example L

Preparation of 3-(4-pyridyl)-5-(formamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLVII using 4-acetylpyridine as the starting material. mp >300° C.; CIMS m/e calc'd for C₁₆H₁₁N₄O₂: 291.0882, found: 291.0882.

Example LI

Preparation of 3-phenyl-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using acetophenone as the starting material. mp>300° C.; CIMS m/e calc'd for C₁₈H₁₃N₃O₂: 304.1065, found: 304.1086.

Example LII

Preparation of 3-(4-methylthiophenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-methylthioacetophenone as the starting material. mp 283° C.; CIMS m/e calc'd for C₁₉H₁₅N₃O₂: 350.0956, found: 350.0963.

Example LIII

Preparation of 3-(4-methylsulphonylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared by oxidation of the product of example LII. mp>300° C.; CIMS m/e calc'd for C₁₉H₁₅N₃O₄S: 382.0860, found: 382.0862.

Example LIV

Preparation of 3-(4-N,N-dimethylaminophenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-N,N,-dimethylaminoacetophenone as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₀H₁₈N₄O₂: 347.1496, found: 347.1508.

Example LV

Preparation of 3-(4-N,N-dimethylaminophenyl)-5-(morpholinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LIV and morpholine as the starting materials. mp>300° C.; CIMS m/e calc'd for C₂₄H₂₆N₅O₃: 432.2036, found: 432.2020.

Example LVI

Preparation of 3-(4-N,N-dimethylaminophenyl)-5-(dimethylaminoacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LIV and dimethylamine as the starting materials. mp>300° C.; CIMS m/e calc'd for C₂₂H₂₄N₅O₂: 390.1930, found: 390.1948.

Example LVII

Preparation of 3-(4-(1-piperidinyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-(1-piperidinyl)acetophenone as the starting material. mp 291° C.; CIMS m/e calc'd for C₂₃H₂₂N₄O₂: 387.1801, found: 387.1821.

Example LVIII

Preparation of 3-(4-morpholinyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-morpholinylacetophenone as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₂H₂₀N₄O₃: 388.1528, found: 388.1535.

Example LIX

Preparation of 3-(4-ethoxyphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-et 288° C.; CIMS m/e calc'd for C₂₀H₁₇N₃O₃: 348.1325, found: 348.1348.

Example LX

Preparation of 3-(4-butylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-butylacetophenone as the starting material. mp 259° C.; CIMS m/e calc'd for C₂₂H₂₁N₃O₂: 360.1701, found: 360.1712.

Example LXI

Preparation of 3-(4-ethylphenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example using 4′-ethylacetophenone as the starting material. mp 294° C.; CIMS m/e calc'd for C₂₀H₁₇N₃O₂: 331.1310, found: 331.1321.

Example LXII

Preparation of 3-(4-n-propylphenyl)-5-(acetamido) indeno [1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example I using 4′-n-propylacetophenone as the starting material. mp 269° C.; CIMS m/e calc'd for C₂₁H₁₉N₃O₂: 346.1555, found: 346.1554.

Example LXIII

Preparation of 3-(4-methoxyphenyl)-5-carbamoylaminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using concentrated ammonium hydroxide as the starting material. mp>300° C.; CIMS m/e calc'd for C₁₈H₁₅N₄O₃: 335.1144, found: 335.1113.

Example LXIV

Preparation of 3-(4-methoxyphenyl)-5-(dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using dimethylamino hydrazine as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₀H₂₀N₅O₃: 378.1566, found: 378.1555.

Example LXV

Preparation of 3-(4-methoxyphenyl)-5-(methylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using methylamine as the starting material. mp>300° C.; CIMS m/e calc'd for C₁₉H17N₄O₃: 349.1300, found: 349.1311.

Example LXVI

Preparation of 3-(4-methoxyphenyl)-5-(morpholinocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using N-aminomorpholine as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₂H₂₂N₅O₄: 420.1671, found: 420.1655.

Example LXVII

Preparation of 3-(4-methoxyphenyl)-5-(cis-2-aminocyclohexanylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using cis-1,2-diaminocyclohexane as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₄H₂₆N₅O₃: 432.2035, found: 432.2020.

Example LXVIII

Preparation of 3-(4-methoxyphenyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XLII using (4-amino)methylpiperazine as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₃H₂₅N₆O₃: 433.1987, found: 433.1999.

Example LXIX

Preparation of 3-(4-methoxyphenyl)-5-(4-uridomethylpiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using example XXX as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₆H₂₉N₆O₄: 489.2250, found: 489.2209.

Example LXX

Preparation of 3-(4-methoxyphenyl)-5-(4-(2-pyridyl)piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(2-pyridyl)piperazine as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₈H₂₇N₆O₃: 495.2144, found: 495.2111.

Example LXXI

Preparation of 3-(4-methoxyphenyl)-5-(4-(aminoethyl)piperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(aminoethyl)piperazine as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₅H₂₉N₆O₃: 461.2300, found: 461.2333.

Example LXXII

Preparation of 3-(4-methoxyphenyl)-5-(4-amidopiperadinylacetamido)indeno[1,2-c)pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using isonipecotamide as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₅H₂₆N₅O₄: 460.1984, found: 460.1998.

Example LXXIII

Preparation of 3-(4-methoxyphenyl)-5-(4-hydroxypiperadinylacetamido)indeno[1,2-c)pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-hydroxypiperadine as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₄H₂₅N₄O₄: 433.1875, found: 433.1844.

Example LXXIV

Preparation of 3-(4-methoxyphenyl)-5-(4-hydroxmethylypiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-hydroxmethylypiperadine as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₅H₂₇N₄O₄: 447.2032, found:447.2002.

Example LXXV

Preparation of 3-(4-methoxyphenyl)-5-(4-amidopiperazinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-amidopiperazine as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₄H₂₅N₆O₆: 493.1835, found:493.1802.

Example LXXVI

Preparation of 3-(4-methoxyphenyl)-5-(4-dimethylaminopiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-dimethylaminopiperadine as the starting material. mp>300° C.; CIMS m/e calc'd for C₂₆H₃₀N₅O₅: 492.2246, found:492.2220.

Example LXXVII

Preparation of 3-(4-methoxyphenyl)-5-(4-aminopiperadinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-aminopiperadine as the starting material. mp >300° C.; CIMS m/e calc'd for C₂₄H₂₆N5O₅: 464.1933, found:464.1975.

Example LXXVIII

Preparation of 3-(4-(dimethylamino)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LIV and 1-methylpiperazine as the starting materials. mp>300° C.; ESI-MS m/e calc'd for C₂₅H₂₉N₆O₂: 445.2352, found: 445.2359.

Example LXXIX

Preparation of 3-(4-(dimethylamino)phenyl)-5-((4-aminomethyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LIV and 4-(aminomethyl)piperidine as the starting materials. ESI-MS m/e calc'd for C₂₆H₃₁N₆O₂: 459.2508, found: 459.2508.

Example LXXX

Preparation of 3-(4-(dimethylamino)phenyl)-5-((4-hydroxy-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LIV and 4-hydroxypiperidine as the starting materials. mp 267° C.; ESI-MS m/e calc'd for C₂₅H₂₈N₅O₃: 446.2192, found: 446.2206.

Example LXXXI

Preparation of 3-(4-(4-morpholinyl)phenyl)-5-(4-morpholinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LVIII and morpholine as the starting materials. mp 258° C.; ESI-MS m/e calc'd for C₂₆H₂₈N₅O₄: 474.2141, found: 474.2151.

Example LXXXII

Preparation of 3-(4-(4-morpholinyl)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LVIII and 1-methylpiperazine as the starting materials. mp 258° C.; ESI-MS m/e calc'd for C₂₇H₃₁N₆O₃: 487.2457, found: 487.2447.

Example LXXXIII

Preparation of 3-(4-(4-morpholinyl)phenyl)-5-((4-hydroxy-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LVIII and 4-hydroxypiperidine as the starting materials. mp 245° C.; ESI-MS m/e calc'd for C₂₇H₃₀N₅O₄: 488.2298, found: 488.2290.

Example LXXXIV

Preparation of 3-(4-(4-morpholinyl)phenyl)-5-((4-aminomethyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples II and XXIII employing the product of example LVIII and 4-(aminomethyl)piperidine as the starting materials. mp 240° C.; ESI-MS m/e calc'd for C₂₈H₃₃N₆O₃: 501.2614, found: 501.2619.

Example LXXXV

Preparation of 3-(4-(dimethylamino)phenyl)-5-((((4-methyl-1-piperazinyl)amino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples I, XXVII, and XLII employing the 4-(dimethylamino)acetophenone and 1-amino-4-methylpiperazine as the starting materials. mp>300° C.; ESI-MS m/e calc'd for C₂₄H₂₈N₇O₂: 446.2304, found: 446.2310.

Example LXXXVI

Preparation of 3-(i-propyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 26 From 3-nitrophthalic Anhydride

A solution of 3-nitrophthalic anhydride (9.7 g, 50 mmol) and 1,1,1-trifluoro-5-methyl-2,4-hexanedione (9.1 g, 50 mmol) in acetic anhydride (28.3 mL, 300 mmol) was treated with triethylamine (13.95 mL, 100 mmol) and stirred at 25° C. for 4 h. The solution was diluted with 1 N HCl (200 mL) and the precipate collected and washed with water (200 mL) and hexane (400 mL) to give the product as a yellow solid (11.1 g, 85%). mp 127-129° C.; CIMS (M+H) calc'd for C₁₃H₁₂NO₅: 262.0715, found: 262.0694.

Step 2. Synthesis of Triketone 27 From 26

A solution of 26 (11 g, 42 mmol) in EtOH (224 mL) and water (56 mL) was treated with zinc (90 g, 1.4 mol) and calcium chloride (3 g, 27 mmol) and heated to reflux for 16 h. The reaction was filtered (Celite) and the filtrate was concentrated at reduced pressure to give an aqueous residue which was extracted with EtOAc (100 mL). The organic layer was separated and washed with sat. EDTA (100 ml) and brine (100 mL), dried (MgSO4), filtered, and concentrated at reduced pressure to give a yellow solid. Trituration with hexane gave the product as a yellow solid (7.1 g, 73%). mp 241-243° C.; CIMS (M+H) calc'd for C₁₃H₁₄NO₃: 232.0974, found: 232.0962.

Step 3. Synthesis of 28 From 27

A solution of 27 (500 mg, 2.16 mmol) in CH2Cl2 (5 mL) was treated with Et3N (0.36 mL, 2.59 mmol) and stirred at 25° C.; for 15 min. The reaction mixture was treated with acetyl chloride (0.18 mL, 2.38 mmol) and stirred at 25° C. for 1 h. The reaction mixture was quenched with 1 N HCl (20 mL) and extracted with EtOAc (20 mL). The organic layer was separated, dried (MgSO4), filtered, and concentrated at reduced pressure to give a brown residue. Trituration with hexane gave the product as a tan solid (484 mg, 82%). mp 241-243° C.; CIMS (M+H) calc'd for C₁₅H₁₆NO₄: 274.1079, found: 274.1093.

Step 4. Synthesis of 29 From 28

A solution of 28 (240 mg, 0.88 mmol) in BuOH (5 mL) was treated with hydrazine hydrate (0.055 mL, 1.76 mmol) and p-TsOH (8.4 mg, 0.044 mmol). The reaction was heated to reflux and stirred for 4 h. The reaction was cooled to 25° C. and the solvent removed at reduced pressure. Recrystalization with i-propyl alcohol gave the product collected as an off-white solid (173 mg, 73%). mp>250° C.; ESIMS (M+H) calc'd for C₁₅H₁₆N₃O₂: 270.1242, found: 270.1258.

Example LXXXVII

Preparation of 3-(c-propyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using the c-propyl analog of 26 as the starting material. mp 220-221° C.; CIMS (M+H) calc'd for C₁₅H₁₄N₃O₂: 268.1086, found: 268.1078.

Example LXXXVIII

Preparation of 3-(t-butyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using the t-butyl analog of 26 as the starting material. mp>250° C.; CIMS (M+H) calc'd for C₁₆H₁₈N₃O₂: 284.1399, found: 284.1395.

Example LXXXIX

Preparation of 3-(2-thienyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using the 2-thienyl analog of 26 as the starting material. mp 269° C.; CIMS (M+H) calc'd for C₁₆H₁₂N₃O₂S: 310.0650, found: 310.0635.

Example XC

Preparation of 3-(3-methyl-2-thienyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using the 3-methyl-2-thienyl analog of 26 as the starting material. mp 275° C.; ESIMS (M+H) calc'd for C₁₇H₁₄N₃O₂S: 324.0811, found: 324.0807.

Example XCI

Preparation of 3-(ethyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the ethyl analog of 15 as the starting materials. mp>250° C.; CIMS (M+H) calc'd for C₁₃H₁₃N₄O₂: 257.1039, found: 257.1033.

Example XCII

Preparation of 3-(n-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the n-propyl analog of 15 as the starting materials. mp 187-189° C.; CIMS (M+H) calc'd for C₁₄H₁₅N₄O₂: 271.1195, found: 271.1187.

Example XCIII

Preparation of 3-(i-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the i-propyl analog of 15 as the starting materials. mp>250° C.; CIMS (M+H) calc'd for C₁₄H₁₅N₄O₂: 271.1195, found: 271.1196.

Example XCIV

Preparation of 3-(c-propyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the c-propyl analog of 15 as the starting materials. mp 252-253° C.; ESIMS (M−H) calc'd for C₁₄H₁₁N₄O₂: 267.0881, found: 267.0884.

Example XCV

Preparation of 3-(c-hexyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the c-hexyl analog of 15 as the starting materials. mp 178-179° C.; ESIMS (M+H) calc'd for C₁₇H₁₉N₄O₂: 311.1507, found: 311.1500.

Example XCVI

Preparation of 3-(2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 2-thienyl analog of 15 as the starting materials. mp 214° C.; CIMS m+calc'd for C₁₅H₁₀N₄O₂S: 310.0517, found: 310.0524.

Example XCVII

Preparation of 3-(3-methyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 3-methyl-2-thienyl analog of 15 as the starting materials. mp 270° C.; ESIMS (M+H) calc'd for C₁₆H₁₃N₄O₂S: 325.0759, found: 325.0744.

Example XCVIII

Preparation of 3-(5-methyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 5-methyl-2-thienyl analog of 15 as the starting materials. mp>280° C.; ESIMS (M+H) calc'd for C₁₆H₁₃N₄O₂S: 325.0759, found: 325.0761.

Example XCIX

Preparation of 3-(5-ethylcarboxyl-2-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 5-ethylcarboxyl-2-thienyl analog of 15 as the starting materials. mp>280° C.; ESIMS (M+H) calc'd for C₁₈H₁₅N₄O₄S: 383.0813, found: 383.0788.

Example C

Preparation of 3-(3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 3-thienyl analog of 15 as the starting materials. mp>280° C.; ESIMS (M+H) calc'd for C₁₅ H₁₁N₄O₂S: 311.0603, found: 311.0594.

Example CI

Preparation of 3-(5-chloro-3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 5-chloro-3-thienyl analog of 15 as the starting materials. mp>300° C.; ESIMS (M+H) calc'd for C₁₅H₁₀N₄O₂SCl: 345.0209, found: 345.0213.

Example CII

Preparation of 3-(2,5-dimethyl-3-thienyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 2,5-dimethyl-3-thienyl analog of 15 as the starting materials. mp>280° C.; ESIMS (M+H) calc'd for C₁₇H₁₅N₄O₂S: 339.0916, found: 339.0905.

Example CIII

Preparation of 3-(2-furanyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 2-furanyl analog of 15 as the starting materials. mp 278° C.; ESIMS (M+H) calc'd for C₁₅H₁₁N₄O₃: 295.0831, found: 295.0838.

Example CIV

Preparation of 3-(i-propyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the i-propyl analog of 15 as the starting materials. mp 231-233° C.; ESIMS (M+H) calc'd for C₁₆H₂₀N₅O₂: 314.1616, found: 314.1599.

Example CV

Preparation of 3-(c-propyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethyihydrazine and the c-propyl analog of 15 as the starting materials. mp XXX° C; ESIMS (M+H) calc'd for C₁₆H₁₈N₅O₂: 312.1460, found: 312.1487.

Example CVI

Preparation of 3-(c-hexyl)-5-(N, N-dimethylaminocarbamoyl)aminoindeno[1,2-c] pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the c-hexyl analog of 15 as the starting materials. mp 229-231° C.; ESIMS (M+H) calc'd for C₁₉H₂₄N₅O₂: 354.1929, found: 354.1932.

Example CVII

Preparation of 3-(2-thienyl)-5-(N, N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using l,1-dimethylhydrazine and the 2-thienyl analog of 15 as the starting materials. mp 279° C.; ESIMS (M+H) calc'd for C₁₇H₁₆N₅O₂S: 354.1024, found: 354.1025.

Example CVIII

Preparation of 3-(5-methoxy-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoideno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 5-methoxy-2-thienyl analog of 15 as the starting materials. mp 280° C.; ESIMS (M+H) calc'd for C₁₈H₁₈N₅O₃S: 384.1130, found: 384.1119.

Example CIX

Preparation of 3-(5-methyl-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 5-methyl-2-thienyl analog of 15 as the starting materials. mp>280° C.; ESIMS (M+H) calc'd for C₁₈H₁₈N₅O₂S: 368.1181, found: 368.1171.

Example CX

Preparation of 3-(5-ethylcarboxyl-2-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 5-ethylcarboxyl-2-thienyl analog of 15 as the starting materials. mp 252° C.; ESIMS (M+H) calc'd for C₂₀H₂₀N₅O₄S: 426.1236, found: 426.1251.

Example CXI

Preparation of 3-(3-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 3-thienyl analog of 15 as the starting materials. mp 202° C.; ESIMS (M+H) calc'd for C₁₇H₁₆N₅O₂S: 354.1025, found: 354.1031.

Example CXII

Preparation of 3-(1-methyl-3-pyrrolyl)-5-(carbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using ammonia and the 1-methyl-3-pyrrolyl analog of 15 as the starting materials. mp>300° C.; ESIMS (M+H) calc'd for C₁₆H₁₄N₅O₂: 308.1147, found: 308.1166.

Example CXIII

Preparation of 3-(2,5-dimethyl-3-thienyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1, 2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 2,5-dimethyl-3-thienyl analog of 15 as the starting materials. mp 252° C.; ESIMS (M+H) calc'd for C₁₉H₂₀N₅O₂S: 382.1338, found: 382.1357.

Example CXIV

Preparation of 3-(2-furanyl)-5-(N,N-dimethylaminocarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1,1-dimethylhydrazine and the 2-furanyl analog of 15 as the starting materials. mp 202° C.; ESIMS (M+H) calc'd for C₁₇H₁₆N₅O₃: 338.1253, found: 338.1248.

Example CXV

Preparation of 3-(i-propyl)-5-(4-carbamoylpiperidinylacetamido)indeno[112-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using isonipecotamide and the i-propyl analog of 14 as the starting materials. mp 224-225° C.; ESIMS (M+H) calc'd for C₂₁H₂₆N₅O₃: 396.2035, found: 396.2036.

Example CXVI

Preparation of 3-(c-hexyl)-5-(4-carbamoylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using isonipecotamide and the c-hexyl analog of 14 as the starting materials. mp 228-229° C.; ESIMS (M+H) calc'd for C₂₄H₃₀N₅O₃: 436.2348, found: 436.2345.

Example CXVII

Preparation of 3-(ethyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(aminomethyl)piperidine and the ethyl analog of 14 as the starting materials. mp 174-176° C.; ESIMS (M+H) calc'd for C₂₀H₂₆N₅O₂: 368.2086, found: 368.2078.

Example CXVIII

Preparation of 3-(i-propyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(aminomethyl)piperidine and the i-propyl analog of 14 as the starting materials. mp 218-220° C.; ESIMS (M+H) calc'd for C₂₁H₂₈N₅O₂: 382.2242, found: 382.2227.

Example CXIX

Preparation of 3-(c-propyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(aminomethyl)piperidine and the c-propyl analog of 14 as the starting materials. mp 138-140° C.; ESIMS (M+H) calc'd for C₂₁H₂₆N₅O₂: 380.2086, found: 380.2079.

Example CXX

Preparation of 3-(c-hexyl)-5-(4-aminomethylpiperidinylacetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example XXIII using 4-(aminomethyl)piperidine and the c-hexyl analog of 14 as the starting materials. mp 196-198° C.; ESIMS (M+H) calc'd for C₂₄H₃₂N₅O₂: 422.2555, found: 422.2540.

Example CXXI

Preparation of 3-(i-propyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1-amino-4-methylpiperazine and the i-propyl analog of 15 as the starting materials. mp 231-233° C.; ESIMS (M+H) calc'd for C₁₉H₂₅N₆O₂: 369.2038, found: 369.2039.

Example CXXII

Preparation of 3-(5-ethylcarboxyl-2-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1-amino-4-methylpiperazine and the 5-ethylcarboxyl-2-thienyl analog of 15 as the starting materials. mp 249° C.; ESIMS (M+H) calc'd for C₂₃H₂₅N₆O₄S: 481.1657, found: 481.1642.

Example CXXIII

Preparation of 3-(5-carboxyl-2-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

A solution of CXXII (30 mg, 0.05 mmol) in 3:1 THF/water (2 mL) was treated with LiOH (23 mg, 0.5 mmol) and the reaction was stirred at 25° C. for 12 h and then heated to reflux for 1 h. The organic solvent was removed at reduced pressure and the residue was partioned between EtOAc (5 mL) and water (5 mL). The organic layer was separated and the aqueous phase was adjusted to pH=2 with 1 M HCl and re-extracted with EtOAc (5mL). The combined organic layers were dried (Na2SO4), filtered and concentrated at reduced pressure to give a crude residue. Purification by reverse phase HPLC gave the product as a yellow solid (10.4 mg, 46%). mp 270° C.; ESIMS (M+H) calc'd for C₂₁H₂₁N₆O₄S: 453.1344, found: 453.1353.

Example CXXIV

Preparation of 3-(2,5-dimethyl-3-thienyl)-5-(4-methylpiperazinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 1-amino-4-methylpiperazine and the 2,5-dimethyl-3-thienyl analog of 15 as the starting materials. mp 250° C.; ESIMS (M+H) calc'd for C₂₂H₂₅N₆O₂S: 437.1760, found: 437.1771.

Example CXXV

Preparation of 3-(i-propyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the i-propyl analog of 15 as the starting materials. mp 256-258° C.; ESIMS (M−H) calc'd for C₁₈H₂₀N₅O₃: 354.1566, found: 354.1543.

Example CXXVI

Preparation of 3-(N-methylcarbamoyl-4-piperidinyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the N-methylcarbamoyl-4-piperidinyl analog of 15 as the starting materials. mp 216-218° C.; ESIMS (M+H) calc'd for C₂₂H₂₇N₆O₅: 455.2042, found: 455.2036.

Example CXXVII

Preparation of 3-(5-methyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the 5-methyl-2-thienyl analog of 15 as the starting materials. mp 261° C.; ESIMS (M+H) calc'd for C₂₀H₂₀N₅O₃S: 410.1287, found: 410.1308.

Example CXXVIII

Preparation of 3-(5-chloro-3-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the 5-chloro-3-thienyl analog of 15 as the starting materials. mp 259° C.; ESIMS (M+H) calc'd for C₁₉H₁₇N₅O₃SCl: 430.0741, found: 430.0757.

Example CXXIX

Preparation of 3-(2,5-dimethyl-3-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the 2,5-dimethyl-3-thienyl analog of 15 as the starting materials. mp>280° C.; ESIMS (M+H) calc'd for C₂₁H₂₂N₅O₃S: 424.1443, found: 424.1431.

Example CXXX

Preparation of 3-(5-ethylcarboxyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI using 4-aminomorpholine and the 5-ethylcarboxyl-2-thienyl analog of 15 as the starting materials. mp 258° C.; ESIMS (M+H) calc'd for C₂₂H₂₂N₅O₅S: 468.1341, found: 468.1331.

Example CXXXIl

Preparation of 3-(5-carboxyl-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI (HYDROLYSIS OF PREVIOUS ESTER). mp 273° C.; ESIMS (M+H) calc'd for C₂₀H₁₈N₅O₅S: 440.1028, found: 440.1026.

Example CXXXII

Preparation of 3-(5-benzylcarboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno1,2-c]pyrazol-4-one

A solution of benzylamine (0.01 mL, 0.09 mmol) in DMF (1 mL) was treated with acid CXXXI (40 mg, 0.09 mmol) and stirred at 25° C. The reaction was treated with TBTU (29 mg, 0.09 mmol) and stirred at 25° C. for 30 min. Triethylamine (0.01 mL, 0.09 mmol) was added and the reaction stirred at 25° C. for 12 h. After adding more TBTU (15 mg, 0.045 mmol) and triethylamine (0.01 mL, 0.09 mmol) the reaction was stirred at 25° C. for an additional 4 h. The reaction was diluted with EtOAc (10 mL) and water (10 mL) and the aqueous layer was extracted with EtOAc (5×10 mL). The combined organic layers were dried (Na2SO4), filtered, and the solvent removed at reduced pressure. Purification of the residue using reverse phase HPLC gave the product as a yellow solid (21 mg, 42%). mp 275° C.; ESIMS (M+H) calc'd for C₂₇H₂₅N₅O₄S: 529.1659, found: 529.1682.

Example CXXXIII

Preparation of 3-(5-(4-methylpiperazinyl) carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1-amino-4-methylpiperazine as the starting material. mp 190° C.; ESIMS (M+H) calc'd for C₂₅H₂₉N₈O₄S: 537.2032, found: 537.2055.

Example CXXXIV

Preparation of 3-(5-(2-(1-methylpyrrolidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 2-(2-aminoethyl)-1-methylpyrrolidine as the starting material. mp 235° C.; ESIMS (M+H) calc'd for C₂₇H₃₂N₇O₄S: 550.2236, found: 550.2229.

Example CXXXV

Preparation of 3-(5-(N,N-dimethylamino)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1,1-dimethylhydrazine as the starting material. mp 201° C.; ESIMS (M+H) calc'd for C₂₂H₂₄N₇O₄S: 482.1610, found: 482.1588.

Example CXXXVI

Preparation of 3-(5-(2-(N,N-dimethylamino)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using N,N-dimethylethylenediamine as the starting material. mp 190° C.; ESIMS (M+H) calc'd for C₂₄H₂₈N₇O₄S: 510.1923, found: 510.1922.

Example CXXXVII

Preparation of 3-(5-(2-(pyrrolidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1-(2-aminoethyl)pyrrolidine as the starting material. mp 224° C.; ESIMS (M+H) calc'd for C₂₆H₃₀N₇O₄S: 536.2080, found: 536.2091.

Example CXXXVIII

Preparation of 3-(5-(2-(morpholinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 4-(2-aminoethyl)morpholine as the starting material. mp 241° C.; ESIMS (M+H) calc'd for C₂₆H₃₀N₇O₅S: 552.2029, found: 552.2043.

Example CXXXIX

Preparation of 3-(5-morpholinylcarboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 4-aminomorpholine as the starting material. mp 271° C.; ESIMS (M+H) calc'd for C₂₄H₂₆N₇O₅S: 524.1716, found: 524.1719.

Example CXL

Preparation of 3-(5-(3-(pyrrolidonyl)propyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1-(3-aminopropyl)-2-pyrrolidinone as the starting material. mp 260° C.; ESIMS (M+H) calc'd for C₂₇H₃₀N₇O₅S: 564.2029, found: 564.2031.

Example CXLI

Preparation of 3-(5-(2-(3-pyridyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fasion as described for example CXXXII using 3-(2-aminoethyl)pyridine as the starting material. mp 203° C.; ESIMS (M+H) cald'd for C₂₇H₂₆N₇O₄S: 544.1766, found: 544.1760.

Example CXLII

Preparation of 3-(5-(3-(imidazolyl)propyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl) aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1-(3-aminopropyl)imidazole as the starting material. mp 263° C.; ESIMS (M+H) calc'd for C₂₆H₂₇N₈O₄S: 547.1875, found: 547.1872.

Example CXLIII

Preparation of 3-(5-(2-(2-pyridyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 2-(2-aminoethyl)pyridine as the starting material. mp>280° C.; ESIMS (M+H) calc'd for C₂₇H₂₆N₇O₄S: 544.1767, found: 544.1778.

Example CXLIV

Preparation of 3-(5-((2-pyridyl)methyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 2-(aminomethyl)pyridine as the starting material. mp 239° C.; ESIMS (M+H) calc'd for C₂₆H₂₄N₇O₄S: 530.1610, found: 530.1603.

Example CXLV

Preparation of 3-(5-(2-(piperidinyl)ethyl)carboxamido-2-thienyl)-5-(morpholinylcarbamoyl)aminoindeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CXXXII using 1-(2-aminoethyl)piperidine as the starting material. mp 228° C.; ESIMS (M+H) calc'd for C₂₇H₃₂N₇O₄S: 550.2236, found: 550.2236.

Example CXLVI

Preparation of 3-(4-(trifluoromethyl)phenyl)-5-(acetamido)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example LXXXVI employing 1-(4-(trifluoromethyl)phenyl)-4,4,4-trifluoro-1,3-butanedione as the starting material. mp>300° C.; ESI⁻-MS m/e calc'd for C₁₉H₁₁N₃O₂: 370.0804, found: 370.0809.

Example CXLVII

Preparation of 3-(4-(4-t-butoxycarbonyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Step 1. Synthesis of 30

A solution of 4-piperazinoacetophenone (24.8 g, 121 mmol) and di-tert-butyl dicarbonate (27.8 g, 128 mmol) in 480 mL of tetrahydrofuran was refluxed for 16 h. After cooling to room temperature the solution was concentrated under vacuum. The resulting solids were washed with hexane and dried under vacuum to afford 29.4 g (80%) of the product as an off-white solid. NMR (CDCl₃) δ7.89 (d, 2 H, J=9 Hz), 6.87 (d, 2 H, J=9 Hz), 3.59 (m, 4 H), 3.33 (m, 4 H), 2.53 (s, 3 H), 1.49 (s, 9 H).

Step 2. Synthesis of 31 From 30

To a solution of 30 (11.35 g, 37 mmol) and ethyl trifluoroacetate (5.40 mL, 45 mmol) in 50 mL of tetrahydrofuran at 25° C. was added dropwise over 15 min. 21% sodium ethoxide in ethanol (16.8 mL, 45 mmol), and the resulting solution then was stirred at 25° C. for 14 h. The reaction mixture was diluted with water, adjusted to pH 5 with conc. hydrochloric acid, and extracted with ethyl acetate. The combined extracts was washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The resulting solid was washed with diethyl ether and dried to furnish 12.1 g (81%) of the product as an orange solid. NMR (CDCl₃) δ7.87 (d, 2 H, J=9 Hz), 6.87 (d, 2 H, J=9 Hz), 6.45 (s, 1 H), 3.60 (m, 4 H), 3.41 (m, 4 H), 1.48 (s, 9 H).

Step 3. Synthesis of CXLVII From 31

Prepared in a similar fashion as described for examples LXXVI and XLII employing 31 and 4-aminomorpholine as starting materials. mp 242° C.; ESI-MS m/e calc'd for C₃₀H₃₆N₇O₅574.2778, found: 574.2762.

Example CXLVIII

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

A solution of CXLVII (0.58 g, 1.0 mmol) in 20 mL of trifluoroacetic acid was stirred at 25° C. for 2 h. The reaction mixture was concentrated under vacuum, and the residue was recrystallized from ethanol to provide 0.53 g (89%) of the yellow product as its TFA-salt. mp 263° C.; ESI-MS m/e calc'd for C₂₅H₂₈N₇O₃: 474.2254, found: 474.2280.

Example CXLIX

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((aminocarbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples XLII and CXLVIII employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII and ammonia as the starting materials. mp 257° C.; ESI-MS m/e calc'd for C₂₁H₂₁N₆O₂: 389.1726, found: 389.1724.

Example CL

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((hydrazinocarbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for examples XLII and CXLVIII employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII and hydrazine as the starting materials. mp 257° C.; ESI-MS m/e calc'd for C₂₁H₂₂N₇O₂: 404.1835, found: 404.1834.

Example CLI

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((dimethylamino)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII as the starting material. Chloroacetylation and treatment with dimethylamine in a similar fashion as described for examples II and XXIII, followed by treatment with hydrazine and removal of the t-butoxycarbonyl group in a similar fashion as described for examples I and CXLVIII, afforded the example compound. mp 243° C.; ESI-MS m/e calc'd for C₂₄H₂₇N₆O₂: 431.2196, found: 431.2198.

Example CLII

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((4-morpholinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII as the starting material. Chloroacetylation and treatment with morpholine in a similar fashion as described for examples II and XXIII, followed by treatment with hydrazine and removal of the t-butoxycarbonyl group in a similar fashion as described for examples I and CXLVIII, afforded the example compound. mp 259° C.; ESI-MS m/e calc'd for C₂₆H₂₉N₆O₃: 473.2301, found: 473.2302.

Example CLIII

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((4-methyl-1-piperazinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII as the starting material. Chloroacetylation and treatment with 1-methylpiperazine in a similar fashion as described for examples II and XXIII, followed by treatment with hydrazine and removal of the t-butoxycarbonyl group in a similar fashion as described for examples I and CXLVIII, afforded the example compound. ESI-MS m/e calc'd for C₂₇H₃₂N₇O₂: 486.2618, found: 486.2608.

Example CLIV

Preparation of 3-(4-(1-piperazinyl)phenyl)-5-((4-aminomethyl-1-piperidinyl)acetamido)indeno[1,2-c]pyrazol-4-one

Prepared employing 2-(4-(4-t-butoxycarbonyl-1-piperazinyl)benzoyl)-4-amino-1,3-indanedione obtained in example CXLVII as the starting material. Chloroacetylation and treatment with 4-(aminomethyl)piperidine in a similar fashion as described for examples II and XXIII, followed by treatment with hydrazine and removal of the t-butoxycarbonyl group in a similar fashion as described for examples I and CXLVIII, afforded the example compound. mp 239° C.; ESI-MS m/e calc'd for C₂₈H₃₄N₇O₂: 500.2774, found: 500.2772.

Example CLV

Preparation of 3-(4-(4-methyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

To a solution of CXLVIII (0.17 g, 0.29 mmol) in 10 mL of methanol and 2 mL of water at 25° C. was added sequentially 37% aqueous formaldehyde (0.45 g, 5.8 mmol), sodium cyanoborohydride (0.18 g, 2.9 mmol), and 4 drops of acetic acid. The resulting solution was stirred at 25° C. for 16 h. The mixture was diluted with water. It then was made acidic (˜pH 1) with conc. hydrochloric acid and stirred for 10 min. The solution next was made basic (˜pH 13) with 50% aqueous sodium hydroxide and finally adjusted to pH 10 with 1 N hydrochloric acid. The mixture was extracted with 4:1 chloroform/isopropanol. The combined extracts were washed with water and brine, dried over anhydrous sodium sulfate, and filtered. To the filtrate was added excess trifluoroacetic acid, and the solution was concentrated under vacuum. The residue was recrystallized from isopropanol to furnish 0.16 g (92%) of the yellow product as its TFA-salt. mp 245° C.; ESI-MS m/e calc'd for C₂₆H₃₀N₇O₃: 488.2410, found: 488.2420.

Example CLVI

Preparation of 3-(4-(4-ethyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLV employing CXLVIII and acetaldehyde as the starting materials. mp 245° C.; ESI-MS m/e calc'd for C₂₇H₃₂N₇O₃: 502.2567, found: 502.2555.

Example CLVII

Preparation of 3-(4-(4-isopropyl-1-piperazinyl)phenyl)-5-(((4-morpholinylamino)carbonyl)amino)indeno[1,2-c]pyrazol-4-one

Prepared in a similar fashion as described for example CLV employing CXLVIII and acetone as the starting materials. mp 253° C.; ESI-MS m/e calc'd for C₂₈H₃₄N₇O₃: 516.2723, found: 516.2726.

UTILITY Inhibition of Kinase/Cyclin Complex Enzymatic Activity

Several of the compounds disclosed in this invention were assayed for their inhibitory activity against cdk4/D1 and cdk2/E kinase complexes. Briefly, the in vitro assays employ cell lysates from insect cells expressing either of the kinases and subsequently their corresponding regulatory units. The cdk2/cyclinE is purified from insect cells expressing His-tagged cdk2 and cyclin E. The cdk/cyclin lysate is combined in a microtitre-type plate along with a kinase compatible buffer, ³²P-labeled ATP at a concentration of 50 mM, a GST-Rb fusion protein and the test compound at varying concentrations. The kinase reaction is allowed to proceeded with the radiolabled ATP, then effectively stopped by the addition of a large excess of EDTA and unlabeled ATP. The GST-Rb labeled protein is sequestered on a GSH-Sepharose bead suspension, washed, resuspended in scintillant, and the ³²P activity detected in a scintillation counter. The compound concentration which inhibits 50% of the kinase activity was calculated for each compound. A compound was considered active if its IC₅₀ was found to be less than 1 μM.

Inhibition of HCT 116 Cancer Cell Proliferation

To test the cellular activity of several compounds disclosed in this invention, we examined the effect of these compounds on cultured HCT116 cells and determined their effect on cell-cycle progression by the calorimetric cytotoxcity test using sulforhodamine B (Skehan et al. J. Natl. Cancer Inst. 82:1107-12, 1990). Briefly, HCT116 cells are cultured in the presence of test compounds at increasing concentrations. At selected time points, groups of cells are fixed with trichloroacetic acid and stained with sulforhodamine B (SRB). Unbound dye was removed by washing and protein-bound dye was extracted for determination of optical density. A compound was considered active if its IC₅₀ was found to be less than 10 μM.

TABLE 1

Example mass mp # R¹ R² (M⁺H) (° C.) I Methyl 4-MeOC₆H₄ 334 268 II ClCH₂ 4-MeOC₆H₄ 382 274 III cyclopropyl 4-MeOC₆H₄ 360 289 IV isopropyl 4-MeOC₆H₄ 362 288 V ethyl 4-MeOC₆H₄ 348 287 VI cyclopentyl 4-MeOC₆H₄ 388 267 VII cyclobutyl 4-MeOC₆H₄ 374 297 VIII benzyl 4-MeOC₆H₄ 410 280 IX n-propyl 4-MeOC₆H₄ 362 282 X 4-ClC₆H₄CH₂ 4-MeOC₆H₄ 444 238 XI 3-MeOC₆H₄CH₂ 4-MeOC₆H₄ 440 >300 XII 4-MeOC₆H₄CH₂ 4-MeOC₆H₄ 440 280 XIII 3,4-diMeOC₆H₄CH₂ 4-MeOC₆H₄ 470 >300 XIV 2,5-diMeOC₆H₄CH₂ 4-MeOC₆H₄ 470 226 XV Methyl 2-MeOC₆H₄ 334 276 XVI Methyl 3,4-diMeOC₆H₄ 364 >300 XVII 3,4- 4-MeOC₆H₄ 454 297 (OCH₂O)C₆H₄CH₂ XVIII 3-thiophenylCH₂ 4-MeOC₆H₄ 416 293 XIX 2-MeOC₆H₄CH₂ 4-MeOC₆H₄ 440 255 XX 3,4-diClOC₆H₄CH₂ 4-MeOC₆H₄ 479 299 XXI 2,4-diClOC₆H₄CH₂ 4-MeOC₆H₄ 479 286 XXII 2-ClC₆H₄CH₂ 4-MeOC₆H₄ 444 300 XXIII H₂NCH₂ 4-MeOC₆H₄ 349 >300 XXIV HOCH₂CH₂NHCH₂ 4-MeOC₆H₄ 393 243 XXV Me₂NCH₂ 4-MeOC₆H₄ 377 279 XXVI piperazinylCH₂ 4-MeOC₆H₄ 418 277 XXVII 4-Me- 4-MeOC₆H₄ 432 >300 piperazinylCH₂ XXVIII 4-HOCH₂CH₂- 4-MeOC₆H₄ 462 >300 piperazinylCH₂ XXIX piperidinylCH₂ 4-MeOC₆H₄ 417 291 XXX 4-NH₂CH₂- 4-MeOC₆H₄ 446 >300 piperidinylCH₂ XXXI CH₃CH₂NHCH₂ 4-MeOC₆H₄ 377 250 XXXII thiomorpholinylCH₂ 4-MeOC₆H₄ 435 298 XXXIII morpholinylCH₂ 4-MeOC₆H₄ 419 295 XXXIV pyrrolidinylCH₂ 4-MeOC₆H₄ 403 279 XXXV 4- 4-MeOC₆H₄ 440 >300 pyridylCH₂NHCH₂ XXXVI 4-CH₃CONHC₆H₄CH₂ 4-MeOC₆H₄ 467 268 XXXVII 4-CH₃OCONHC₆H₄CH₂ 4-MeOC₆H₄ 483 257 XXXVIII 4-NH₂CH₂CONHC₆H₄CH₂ 4-MeOC₆H₄ 482 228 XXXIX 4-Me₂NCH₂CONHC₆H₄CH₂ 4-MeOC₆H₄ 510 >300 XL 4-N₃C₆H₄CH₂ 4-MeOC₆H₄ 451 >300 XLI 4-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 425 283 XLII C₆H₅NH 4-MeOC₆H₄ 411 >300 XLIII CH₃CH₂CH₂NH 4-MeOC₆H₄ 377 252 XLIV 4-NH₂C₆H₄CH₂NH 4-MeOC₆H₄ 440 >300 XLV 4-pyridylCH₂NH 4-MeOC₆H₄ 426 >300 XLVI Methyl 4-HOC₆H₄ 320 >300 XLVII H 4-MeOC₆H₄ 320 280 XLVIII Methyl 3-pyridyl 305 >300 XLIX Methyl 4-pyridyl 305 >300 L H 4-pyridyl 291 >300 LI Methyl C₆H₅ 305 >300 LII Methyl 4-MeSC₆H₄ 351 283 LIII Methyl 4-MeSO₂C₆H₄ 383 >300 LVI Methyl 4-Me₂NC₆H₄ 348 >300 LV morpholinylCH₂ 4-Me₂NC₆H₄ 432 >300 LVI Me₂NCH₂ 4-Me₂NC₆H₄ 390 >300 LVII Methyl 4-(piperdinyl)C₆H₄ 388 291 LVIII Methyl 4- 389 >300 (morpholinyl)C₆H₄ LIX Methyl 4-CH₃CH₂OC₆H₄ 349 288 LX Methyl 4-CH₃CH₂CH₂CH₂C₆H₄ 361 259 LXI Methyl 4-CH₃CH₂C₆H₄ 332 294 LXII Methyl 4-CH₃CH₂CH₂C₆H₄ 347 269 LXIII NH₂ 4-MeOC₆H₄ 335 >300 LXIV Me2NNH 4-MeOC₆H₄ 378 >300 LXV MeNH 4-MeOC₆H₄ 349 >300 LXVI morpholinylNH 4-MeOC₆H₄ 420 >300 LXVII cis-1,2- 4-MeOC₆H₄ 432 >300 diaminocyclohexanyl LXVIII 4- 4-MeOC₆H₄ 433 >300 methylpiperazinylNH LXVIX 4- 4-MeOC₆H₄ 489 >300 uridomethylpiperadinylCH₂ LXX 4-(2- 4-MeOC₆H₄ 495 >300 pyridyl)piperazinyl CH₂ LXXI 4- 4-MeOC₆H₄ 461 >300 (aminoethyl)piperazinyl CH₂ LXXII 4-amidopiperidinylCH₂ 4-MeOC₆H₄ 460 >300 LXXIII 4- 4-MeOC₆H₄ 433 >300 hydroxypiperidinylCH₂ LXXIV 4- 4-MeOC₆H₄ 447 >300 hydroxymethylpiperidinylCH₂ LXXV 4-amidopiperazinylCH₂ 4-MeOC₆H₄ 493 >300 LXXVI 4- 4-MeOC₆H₄ 492 >300 dimethylaminopiperadinylCH₂ LXXVII 4-aminopiperadinylCH₂ 4-MeOC₆H₄ 464 >300 LXXVIII 4-Me-piperazinylCH₂ 4-Me₂NC₆H₄ 445 >300 LXXIX 4-NH₂CH₂- 4-Me₂NC₆H₄ 459 NA piperidinylCH₂ LXXX 4-OH-piperidinylCH₂ 4-Me₂NC₆H₄ 446 267 LXXXI morpholinylCH₂ 4- 474 258 (morpholinyl)C₆H₄ LXXXII 4-Me-piperazinylCH₂ 4- 487 258 (morpholinyl)C₆H₄ LXXXIII 4-OH-piperidinylCH₂ 4- 488 245 (morpholinyl)C₆H₄ LXXXIV 4-NH₂CH₂- 4- 501 240 piperidinylCH₂ (morpholinyl)C₆H₄ LXXXV 4-Me-piperazinylNH 4-Me₂NC₆H₄ 446 >300 LXXXVI Methyl i-propyl 270 >250 LXXXVII Methyl c-propyl 268 220 LXXXVIII Methyl t-butyl 284 >250 LXXXIX Methyl 2-thienyl 310 269 XC Methyl 3-Me-2-thienyl 324 275 XCI NH₂ Ethyl 257 >250 XCII NH₂ n-propyl 271 187 XCIII NH₂ i-propyl 271 >250 XCIV NH₂ c-propyl 267 252 (M − H) XCV NH₂ c-hexyl 311 178 XCVI NH₂ 2-thienyl 310 214 (M+) XCVII NH₂ 3-Me-2-thienyl 325 270 XCVIII NH₂ 5-Me-2-thienyl 325 >280 XCIX NH₂ 5-CO₂Et-2-thienyl 383 >280 C NH₂ 3-thienyl 311 >280 CI NH₂ 5-Cl-3-thienyl 345 >300 CII NH₂ 2,5-diMe-3-thienyl 339 >280 CIII NH₂ 2-furanyl 295 278 CIV Me₂NNH i-propyl 314 231 CV Me₂NNH c-propyl 312 CVI Me₂NNH c-hexyl 354 229 CVII Me₂NNH 2-thienyl 354 279 CVIII Me₂NNH 5-MeO-2-thienyl 384 280 CIX Me₂NNH 5-Me-2-thienyl 368 >280 CX Me₂NNH 5-CO₂Et-2-thienyl 426 252 CXI Me₂NNH 3-thienyl 354 202 CXII NH₂ 1-methyl-3- 308 >300 pyrrolyl CXIII Me₂NNH 2,5-diMe-3-thienyl 382 252 CXIV Me₂NNH 2-furanyl 338 202 CXV 4-NH₂CO- i-propyl 396 224 piperidinylCH₂ CXVI 4-NH₂CO- c-hexyl 436 228 piperidinylCH₂ CXVII 4-NH₂CH₂- ethyl 368 174 piperidinylCH₂ CXVIII 4-NH₂CH₂- i-propyl 382 218 piperidinylCH₂ CXVIX 4-NH₂CH₂- c-propyl 380 138 piperidinyl CH₂ CXX 4-NH₂CH₂- c-hexyl 422 196 piperidinylCH₂ CXXI 4-CH₃-piperazinylNH i-propyl 369 231 CXXII 4-CH₃-piperazinylNH 5-CO₂Et-2-thienyl 481 249 CXXIII 4-CH₃-piperazinylNH 5-CO₂H-2-thienyl 453 270 CXXIV 4-CH₃-piperazinylNH 2,5-diMe-3-thienyl 437 250 CXXV morpholinylNH i-propyl 354 256 (M − H) CXXVI morpholinylNH 4-CO₂Me- 455 216 piperidinyl CXXVII morpholinylNH 5-Me-2-thienyl 410 261 CXXVIII morpholinylNH 5-Cl-3-thienyl 430 259 CXXIX morpholinylNH 2,5-diMe-3-thienyl 424 >280 CXXX morpholinylNH 5-CO₂Et-2-thienyl 468 258 CXXXI morpholinylNH 5-CO₂H-2-thienyl 440 273 CXXXII morpholinylNH 5-CONHBn-2-thienyl 529 275 CXXXIII morpholinylNH 5-CONH(4-Me- 537 190 piperazinyl)-2- thienyl CXXXIV morpholinylNH 5-CONHCH₂CH₂(1-Me- 550 235 2-pyrrolidinyl)-2- thienyl CXXXV morpholinylNH 5-CONHNMe₂-2- 482 201 thienyl CXXXVI morpholinylNH 5-CONHCH₂CH₂NMe₂- 510 190 2-thienyl CXXXVII morpholinylNH 5-CONHCH₂CH₂(1- 536 224 pyrrolidinyl)-2- thienyl CXXXVIII tnorpholinylNH 5-CONHCH₂CH₂(1- 552 241 morpholinyl)-2- thienyl CXXXIX morpholinylNH 5-CoNHmorpholinyl- 524 271 2-thienyl CXL morpholinylNH 5-CONHCH₂CH₂CH₂(1- 564 260 pyrrolidonyl)-2- thienyl CXLI morpholinylNH 5-CONHCH₂CH₂(3- 544 203 pyridyl)-2-thienyl CXLII morpholinylNH 5-CONHCH₂CH₂CH₂(1- 547 263 imidazolyl)-2- thienyl CXLIII morpholinylNH 5-CONHCH₂CH₂(2- 544 >280 pyridyl)-2-thienyl CXLIV morpholinylNH 5-CONHCH₂(3- 530 239 pyridyl)-2-thienyl CXLV morpholinylNH 5-CONHCH₂CH₂(1- 550 228 piperidinyl)-2- thienyl CXLVI Methyl 4-CF₃C₆H₄ 370 >300 (M − H)⁻ CXLVII morpholinylNH 4-(4-Boc- 574 242 piperazinyl)C₆H₄ CXLVIII morpholinylNH 4- 474 263 (piperazinyl)C₆H₄ CXLIX NH₂ 4- 389 257 (piperazinyl)C₆H₄ CL NH₂NH 4- 404 257 (piperazinyl)C₆H₄ CLI Me₂NCH₂ 4- 431 243 (piperazinyl)C₆H₄ CLII morpholinylCH₂ 4- 473 259 (piperazinyl)C₆H₄ CLIII 4-Me-piperazinylCH₂ 4- 486 NA (piperazinyl)C₆H₄ CLIV 4-NH₂CH₂- 4- 500 239 piperidinylCH₂ (piperazinyl)C₆H₄ CLV morpholinylNH 4-(4-Me- 488 245 piperazinyl)C₆H₄ CLVI morpholinylNH 4-(4-Et- 502 245 piperazinyl)C₆H₄ CLVII morpholinylNH 4-(4-i-Pr- 516 253 piperazinyl)C₆H₄

TABLE 2

Example Number R¹ R² 100 2-pyridylmethyl 4-MeOC₆H₄ 101 2-pyridylmethyl 3-MeOC₆H₄ 102 2-pyridylmethyl 4-NH₂C₆H₄ 103 2-pyridylmethyl 3-NH₂C₆H₄ 104 2-pyridylmethyl 2-NH₂C₆H₄ 105 2-pyridylmethyl 4-Me₂NC₆H₄ 106 2-pyridylmethyl 3-Me₂NC₆H₄ 107 2-pyridylmethyl 2-Me₂NC₆H₄ 108 2-pyridylmethyl 4-pyridyl 109 2-pyridylmethyl 3-pyridyl 110 2-pyridylmethyl 2-pyridyl 111 2-pyridylmethyl 2-thiazolyl 112 2-pyridylmethyl 2-pyrazolyl 113 2-pyridylmethyl 5-isoquinolyl 114 2-pyridylmethyl 3,4- methylenedioxyC₆H₃ 115 2-pyridylmethyl 3,4- ethylenedioxyC₆H₃ 116 2-pyridylmethyl 2-imidazolyl 117 2-pyridylmethyl 2-oxazolyl 118 2-pyridylmethyl 4-isoxazolyl 119 2-pyridylmethyl 4-HOC₆H₄ 120 2-pyridylmethyl 3-HOC₆H₄ 121 2-pyridylmethyl 3,4-diHOC₆H₄ 122 2-pyridylmethyl 4-NH₂CH₂C₆H₄ 123 2-pyridylmethyl 3-NH₂CH₂C₆H₄ 124 3-pyridylmethyl 4-MeOC₆H₄ 125 3-pyridylmethyl 3-MeOC₆H₄ 126 3-pyridylmethyl 4-NH₂C₆H₄ 127 3-pyridylmethyl 3-NH₂C₆H₄ 128 3-pyridylmethyl 2-NH₂C₆H₄ 129 3-pyridylmethyl 4-Me₂NC₆H₄ 130 3-pyridylmethyl 3-Me₂NC₆H₄ 131 3-pyridylmethyl 2-Me₂NC₆H₄ 132 3-pyridylmethyl 4-pyridyl 133 3-pyridylmethyl 3-pyridyl 134 3-pyridylmethyl 2-pyridyl 135 3-pyridylmethyl 2-thiazolyl 136 3-pyridylmethyl 2-pyrazolyl 137 3-pyridylmethyl 5-isoquinolyl 138 3-pyridylmethyl 3,4- methylenedioxyC₆H₃ 139 3-pyridylmethyl 3,4- ethylenedioxyC₆H₃ 140 3-pyridylmethyl 2-imidazolyl 141 3-pyridylmethyl 2-oxazolyl 142 3-pyridylmethyl 4-isoxazolyl 143 3-pyridylmethyl 4-HOC₆H₄ 144 3-pyridylmethyl 3-HOC₆H₄ 145 3-pyridylmethyl 3,4-diHOC₆H₄ 146 3-pyridylmethyl 4-NH₂CH₂C₆H₄ 147 3-pyridylmethyl 3-NH₂CH₂C₆H₄ 148 4-pyridylmethyl 4-MeOC₆H₄ 149 4-pyridylmethyl 3-MeOC₆H₄ 150 4-pyridylmethyl 4-NH₂C₆H₄ 151 4-pyridylmethyl 3-NH₂C₆H₄ 152 4-pyridylmethyl 2-NH₂C₆H₄ 153 4-pyridylmethyl 4-Me₂NC₆H₄ 154 4-pyridylmethyl 3-Me₂NC₆H₄ 155 4-pyridylmethyl 2-Me₂NC₆H₄ 156 4-pyridylmethyl 4-pyridyl 157 4-pyridylmethyl 3-pyridyl 158 4-pyridylmethyl 2-pyridyl 159 4-pyridylmethyl 2-thiazolyl 160 4-pyridylmethyl 2-pyrazolyl 161 4-pyridylmethyl 5-isoquinolyl 162 4-pyridylmethyl 3,4- methylenedioxyC₆H₃ 163 4-pyridylmethyl 3,4- ethylenedioxyC₆H₃ 164 4-pyridylmethyl 2-imidazolyl 165 4-pyridylmethyl 2-oxazolyl 166 4-pyridylmethyl 4-isoxazolyl 167 4-pyridylmethyl 4-HOC₆H₄ 168 4-pyridylmethyl 3-HOC₆H₄ 169 4-pyridylmethyl 3,4-diHOC₆H₄ 170 4-pyridylmethyl 4-NH₂CH₂C₆H₄ 171 4-pyridylmethyl 3-NH₂CH₂C₆H₄ 172 2-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 173 2-NH₂C₆H₄CH₂ 3-MeOC₆H₄ 174 2-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 175 2-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 176 2-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 177 2-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 178 2-NH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 179 2-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 180 2-NH₂C₆H₄CH₂ 4-pyridyl 181 2-NH₂C₆H₄CH₂ 3-pyridyl 182 2-NH₂C₆H₄CH₂ 2-pyridyl 183 2-NH₂C₆H₄CH₂ 2-thiazolyl 184 2-NH₂C₆H₄CH₂ 2-pyrazolyl 185 2-NH₂C₆H₄CH₂ 5-isoquinolyl 186 2-NH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 187 2-NH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 188 2-NH₂C₆H₄CH₂ 2-imidazolyl 189 2-NH₂C₆H₄CH₂ 2-oxazolyl 190 2-NH₂C₆H₄CH₂ 4-isoxazolyl 191 2-NH₂C₆H₄CH₂ 4-HOC₆H₄ 192 2-NH₂C₆H₄CH₂ 3-HOC₆H₄ 193 2-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 194 2-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 195 2-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 196 3-NH₂C₆H₄CH₂ 3-MeOC₆H₄ 197 3-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 198 3-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 199 3-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 200 3-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 201 3-NH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 202 3-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 203 3-NH₂C₆H₄CH₂ 4-pyridyl 204 3-NH₂C₆H₄CH₂ 3-pyridyl 205 3-NH₂C₆H₄CH₂ 2-pyridyl 206 3-NH₂C₆H₄CH₂ 2-thiazolyl 207 3-NH₂C₆H₄CH₂ 2-pyrazolyl 208 3-NH₂C₆H₄CH₂ 5-isoquinolyl 209 3-NH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 210 3-NH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 211 3-NH₂C₆H₄CH₂ 2-imidazolyl 212 3-NH₂C₆H₄CH₂ 2-oxazolyl 213 3-NH₂C₆H₄CH₂ 4-isoxazolyl 214 3-NH₂C₆H₄CH₂ 4-HOC₆H₄ 215 3-NH₂C₆H₄CH₂ 3-HOC₆H₄ 216 3-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 217 3-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 218 3-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 219 4-NH₂C₆H₄CH₂ 3-MeOC₆H₄ 220 4-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 221 4-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 222 4-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 223 4-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 224 4-NH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 225 4-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 226 4-NH₂C₆H₄CH₂ 4-pyridyl 227 4-NH₂C₆H₄CH₂ 3-pyridyl 228 4-NH₂C₆H₄CH₂ 2-pyridyl 229 4-NH₂C₆H₄CH₂ 2-thiazolyl 230 4-NH₂C₆H₄CH₂ 2-pyrazolyl 231 4-NH₂C₆H₄CH₂ 5-isoquinolyl 232 4-NH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 233 4-NH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 234 4-NH₂C₆H₄CH₂ 2-imidazolyl 235 4-NH₂C₆H₄CH₂ 2-oxazolyl 236 4-NH₂C₆H₄CH₂ 4-isoxazolyl 237 4-NH₂C₆H₄CH₂ 4-HOC₆H₄ 238 4-NH₂C₆H₄CH₂ 3-HOC₆H₄ 239 4-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 240 4-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 241 4-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 242 2-MeOC₆H₄CH₂ 3-MeOC₆H₄ 243 2-MeOC₆H₄CH₂ 4-NH₂C₆H₄ 244 2-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 245 2-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 246 2-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 247 2-MeOC₆H₄CH₂ 3-Me₂NC₆H₄ 248 2-MeOC₆H₄CH₂ 2-Me₂NC₆H₄ 249 2-MeOC₆H₄CH₂ 4-pyridyl 250 2-MeOC₆H₄CH₂ 3-pyridyl 251 2-MeOC₆H₄CH₂ 2-pyridyl 252 2-MeOC₆H₄CH₂ 2-thiazolyl 253 2-MeOC₆H₄CH₂ 2-pyrazolyl 254 2-MeOC₆H₄CH₂ 5-isoquinolyl 255 2-MeOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 256 2-MeOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 257 2-MeOC₆H₄CH₂ 2-imidazolyl 258 2-MeOC₆H₄CH₂ 2-oxazolyl 259 2-MeOC₆H₄CH₂ 4-isoxazolyl 260 2-MeOC₆H₄CH₂ 4-HOC₆H₄ 261 2-MeOC₆H₄CH₂ 3-HOC₆H₄ 262 2-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 263 2-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 264 2-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 265 3-MeOC₆H₄CH₂ 3-MeOC₆H₄ 266 3-MeOC₆H₄CH₂ 4-NH₂C₆H₄ 267 3-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 268 3-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 269 3-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 270 3-MeOC₆H₄CH₂ 3-Me₂NC₆H₄ 271 3-MeOC₆H₄CH₂ 2-Me₂NC₆H₄ 272 3-MeOC₆H₄CH₂ 4-pyridyl 273 3-MeOC₆H₄CH₂ 3-pyridyl 274 3-MeOC₆H₄CH₂ 2-pyridyl 275 3-MeOC₆H₄CH₂ 2-thiazolyl 276 3-MeOC₆H₄CH₂ 2-pyrazolyl 277 3-MeOC₆H₄CH₂ 5-isoquinolyl 278 3-MeOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 279 3-MeOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 280 3-MeOC₆H₄CH₂ 2-imidazolyl 281 3-MeOC₆H₄CH₂ 2-oxazolyl 282 3-MeOC₆H₄CH₂ 4-isoxazolyl 283 3-MeOC₆H₄CH₂ 4-HOC₆H₄ 284 3-MeOC₆H₄CH₂ 3-HOC₆H₄ 285 3-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 286 3-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 287 3-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 288 4-MeOC₆H₄CH₂ 3-MeOC₆H₄ 289 4-MeOC₆H₄CH₂ 4-NH₂C₆H₄ 290 4-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 291 4-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 292 4-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 293 4-MeOC₆H₄CH₂ 3-Me₂NC₆H₄ 294 4-MeOC₆H₄CH₂ 2-Me₂NC₆H₄ 295 4-MeOC₆H₄CH₂ 4-pyridyl 296 4-MeOC₆H₄CH₂ 3-pyridyl 297 4-MeOC₆H₄CH₂ 2-pyridyl 298 4-MeOC₆H₄CH₂ 2-thiazolyl 299 4-MeOC₆H₄CH₂ 2-pyrazolyl 300 4-MeOC₆H₄CH₂ 5-isoquinolyl 301 4-MeOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 302 4-MeOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 303 4-MeOC₆H₄CH₂ 2-imidazolyl 304 4-MeOC₆H₄CH₂ 2-oxazolyl 305 4-MeOC₆H₄CH₂ 4-isoxazolyl 306 4-MeOC₆H₄CH₂ 4-HOC₆H₄ 307 4-MeOC₆H₄CH₂ 3-HOC₆H₄ 308 4-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 309 4-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 310 4-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 311 2-HOC₆H₄CH₂ 4-MeOC₆H₄ 312 2-HOC₆H₄CH₂ 3-MeOC₆H₄ 313 2-HOC₆H₄CH₂ 4-NH₂C₆H₄ 314 2-HOC₆H₄CH₂ 3-NH₂C₆H₄ 315 2-HOC₆H₄CH₂ 2-NH₂C₆H₄ 316 2-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 317 2-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 318 2-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 319 2-HOC₆H₄CH₂ 4-pyridyl 320 2-HOC₆H₄CH₂ 3-pyridyl 321 2-HOC₆H₄CH₂ 2-pyridyl 322 2-HOC₆H₄CH₂ 2-thiazolyl 323 2-HOC₆H₄CH₂ 2-pyrazolyl 324 2-HOC₆H₄CH₂ 5-isoquinolyl 325 2-HOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 326 2-HOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 327 2-HOC₆H₄CH₂ 2-imidazolyl 328 2-HOC₆H₄CH₂ 2-oxazolyl 329 2-HOC₆H₄CH₂ 4-isoxazolyl 330 2-HOC₆H₄CH₂ 4-HOC₆H₄ 331 2-HOC₆H₄CH₂ 3-HOC₆H₄ 332 2-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 333 2-HOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 334 2-HOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 335 3-HOC₆H₄CH₂ 4-MeOC₆H₄ 336 3-HOC₆H₄CH₂ 3-MeOC₆H₄ 337 3-HOC₆H₄CH₂ 4-NH₂C₆H₄ 338 3-HOC₆H₄CH₂ 3-NH₂C₆H₄ 339 3-HOC₆H₄CH₂ 2-NH₂C₆H₄ 340 3-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 341 3-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 342 3-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 343 3-HOC₆H₄CH₂ 4-pyridyl 344 3-HOC₆H₄CH₂ 3-pyridyl 345 3-HOC₆H₄CH₂ 2-pyridyl 346 3-HOC₆H₄CH₂ 2-thiazolyl 347 3-HOC₆H₄CH₂ 2-pyrazolyl 348 3-HOC₆H₄CH₂ 5-isoquinolyl 349 3-HOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 350 3-HOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 351 3-HOC₆H₄CH₂ 2-imidazolyl 352 3-HOC₆H₄CH₂ 2-oxazolyl 353 3-HOC₆H₄CH₂ 4-isoxazolyl 354 3-HOC₆H₄CH₂ 4-HOC₆H₄ 355 3-HOC₆H₄CH₂ 3-HOC₆H₄ 356 3-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 357 3-HOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 358 3-HOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 359 4-HOC₆H₄CH₂ 4-MeOC₆H₄ 360 4-HOC₆H₄CH₂ 3-MeOC₆H₄ 361 4-HOC₆H₄CH₂ 4-NH₂C₆H₄ 362 4-HOC₆H₄CH₂ 3-NH₂C₆H₄ 363 4-HOC₆H₄CH₂ 2-NH₂C₆H₄ 364 4-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 365 4-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 366 4-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 367 4-HOC₆H₄CH₂ 4-pyridyl 368 4-HOC₆H₄CH₂ 3-pyridyl 369 4-HOC₆H₄CH₂ 2-pyridyl 370 4-HOC₆H₄CH₂ 2-thiazolyl 371 4-HOC₆H₄CH₂ 2-pyrazolyl 372 4-HOC₆H₄CH₂ 5-isoquinolyl 373 4-HOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 374 4-HOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 375 4-HOC₆H₄CH₂ 2-imidazolyl 376 4-HOC₆H₄CH₂ 2-oxazolyl 377 4-HOC₆H₄CH₂ 4-isoxazolyl 378 4-HOC₆H₄CH₂ 4-HOC₆H₄ 379 4-HOC₆H₄CH₂ 3-HOC₆H₄ 380 4-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 381 4-HOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 382 4-HOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 383 4-ClC₆H₄CH₂ 3-MeOC₆H₄ 384 4-ClC₆H₄CH₂ 4-NH₂C₆H₄ 385 4-ClC₆H₄CH₂ 3-NH₂C₆H₄ 386 4-ClC₆H₄CH₂ 2-NH₂C₆H₄ 387 4-ClC₆H₄CH₂ 4-Me₂NC₆H₄ 388 4-ClC₆H₄CH₂ 3-Me₂NC₆H₄ 389 4-ClC₆H₄CH₂ 2-Me₂NC₆H₄ 390 4-ClC₆H₄CH₂ 4-pyridyl 391 4-ClC₆H₄CH₂ 3-pyridyl 392 4-ClC₆H₄CH₂ 2-pyridyl 393 4-ClC₆H₄CH₂ 2-thiazolyl 394 4-ClC₆H₄CH₂ 2-pyrazolyl 395 4-ClC₆H₄CH₂ 5-isoquinolyl 396 4-ClC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 397 4-ClC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 398 4-ClC₆H₄CH₂ 2-imidazolyl 399 4-ClC₆H₄CH₂ 2-oxazolyl 400 4-ClC₆H₄CH₂ 4-isoxazolyl 401 4-ClC₆H₄CH₂ 4-HOC₆H₄ 402 4-ClC₆H₄CH₂ 3-HOC₆H₄ 403 4-ClC₆H₄CH₂ 3,4-diHOC₆H₄ 404 4-ClC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 405 4-ClC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 406 2-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 407 2-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 408 2-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 409 2-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 410 2-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 411 2-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 412 2-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 413 2-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 414 2-NH₂CH₂C₆H₄CH₂ 4-pyridyl 415 2-NH₂CH₂C₆H₄CH₂ 3-pyridyl 416 2-NH₂CH₂C₆H₄CH₂ 2-pyridyl 417 2-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 418 2-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 419 2-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 420 2-NH₂CH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 421 2-NH₂CH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 422 2-NH₂CH₂C₆H₄CH₂ 2-imidazolyl 423 2-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 424 2-NH₂CH₂C₆H₄CH₂ 4-isoxazolyl 425 2-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 426 2-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄ 427 2-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 428 2-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 429 2-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 430 3-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 431 3-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 432 3-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 433 3-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 434 3-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 435 3-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 436 3-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 437 3-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 438 3-NH₂CH₂C₆H₄CH₂ 4-pyridyl 439 3-NH₂CH₂C₆H₄CH₂ 3-pyridyl 440 3-NH₂CH₂C₆H₄CH₂ 2-pyridyl 441 3-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 442 3-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 443 3-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 444 3-NH₂CH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 445 3-NH₂CH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 446 3-NH₂CH₂C₆H₄CH₂ 2-imidazolyl 447 3-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 448 3-NH₂CH₂C₆H₄CH₂ 4-isoxazolyl 449 3-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 450 3-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄ 451 3-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 452 3-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 453 3-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 454 4-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 455 4-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 456 4-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 457 4-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 458 4-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 459 4-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 460 4-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 461 4-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 462 4-NH₂CH₂C₆H₄CH₂ 4-pyridyl 463 4-NH₂CH₂C₆H₄CH₂ 3-pyridyl 464 4-NH₂CH₂C₆H₄CH₂ 2-pyridyl 465 4-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 466 4-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 467 4-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 468 4-NH₂CH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 469 4-NH₂CH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 470 4-NH₂CH₂C₆H₄CH₂ 2-imidazolyl 471 4-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 472 4-NH₂CH₂C₆H₄CH₂ 4-isoxazolyl 473 4-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 474 4-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄ 475 4-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 476 4-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 477 4-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 478 2-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 479 2-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 480 2-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 481 2-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 482 2-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 483 2-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 484 2-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 485 2-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 486 2-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 487 2-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 488 2-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 489 2-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 490 2-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 491 2-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 492 2-Me₂NCH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 493 2-Me₂NCH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 494 2-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 495 2-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 496 2-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 497 2-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 498 2-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 499 2-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 500 2-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 501 2-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 502 3-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 503 3-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 504 3-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 505 3-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 506 3-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 507 3-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 508 3-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 509 3-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 510 3-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 511 3-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 512 3-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 513 3-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 514 3-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 515 3-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 516 3-Me₂NCH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 517 3-Me₂NCH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 518 3-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 519 3-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 520 3-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 521 3-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 522 3-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 523 3-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 524 3-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 525 3-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 526 4-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 527 4-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 528 4-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 529 4-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 530 4-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 531 4-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 532 4-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 533 4-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 534 4-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 535 4-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 536 4-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 537 4-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 538 4-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 539 4-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 540 4-Me₂NCH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 541 4-Me₂NCH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 542 4-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 543 4-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 545 4-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 546 4-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 547 4-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 548 4-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 549 4-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 550 4-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 551 H 3-MeOC₆H₄ 552 H 4-NH₂C₆H₄ 553 H 3-NH₂C₆H₄ 554 H 2-NH₂C₆H₄ 555 H 4-Me₂NC₆H₄ 556 H 3-Me₂NC₆H₄ 557 H 2-Me₂NC₆H₄ 558 H 3-pyridyl 559 H 2-pyridyl 560 H 2-thiazolyl 561 H 2-pyrazolyl 562 H 5-isoquinolyl 563 H 3,4- methylenedioxyC₆H₃ 564 H 3,4- ethylenedioxyC₆H₃ 565 H 2-imidazolyl 566 H 2-oxazolyl 567 H 4-isoxazolyl 568 H 4-HOC₆H₄ 569 H 3-HOC₆H₄ 570 H 3,4-diHOC₆H₄ 571 H 4-NH₂CH₂C₆H₄ 572 H 3-NH₂CH₂C₆H₄ 573 Me 3-MeOC₆H₄ 574 Me 4-NH₂C₆H₄ 575 Me 3-NH₂C₆H₄ 576 Me 2-NH₂C₆H₄ 577 Me 4-Me₂NC₆H₄ 578 Me 3-Me₂NC₆H₄ 579 Me 2-Me₂NC₆H₄ 580 Me 3-pyridyl 581 Me 2-pyridyl 582 Me 2-thiazolyl 583 Me 2-pyrazolyl 584 Me 5-isoquinolyl 585 Me 3,4- ethylenedioxyC₆H₃ 586 Me 2-imidazolyl 587 Me 2-oxazolyl 588 Me 4-isoxazolyl 589 Me 3-HOC₆H₄ 590 Me 3,4-diHOC₆H₄ 591 Me 4-NH₂CH₂C₆H₄ 592 Me 3-NH₂CH₂C₆H₄ 593 Et 3-MeOC₆H₄ 594 Et 4-NH₂C₆H₄ 595 Et 3-NH₂C₆H₄ 596 Et 2-NH₂C₆H₄ 597 Et 4-Me₂NC₆H₄ 598 Et 3-Me₂NC₆H₄ 599 Et 2-Me₂NC₆H₄ 600 Et 4-pyridyl 601 Et 3-pyridyl 601 Et 2-pyridyl 603 Et 2-thiazolyl 604 Et 2-pyrazolyl 605 Et 5-isoquinolyl 606 Et 3,4- methylenedioxyC₆H₃ 607 Et 3,4- ethylenedioxyC₆H₃ 608 Et 2-imidazolyl 609 Et 2-oxazolyl 610 Et 4-isoxazolyl 611 Et 4-HOC₆H₄ 612 Et 3-HOC₆H₄ 613 Et 3,4-diHOC₆H₄ 614 Et 4-NH₂CH₂C₆H₄ 615 Et 3-NH₂CH₂C₆H₄ 616 Me₂NCH₂ 3-MeOC₆H₄ 617 Me₂NCH₂ 4-NH₂C₆H₄ 618 Me₂NCH₂ 3-NH₂C₆H₄ 619 Me₂NCH₂ 2-NH₂C₆H₄ 620 Me₂NCH₂ 4-Me₂NC₆H₄ 621 Me₂NCH₂ 3-Me₂NC₆H₄ 622 Me₂NCH₂ 2-Me₂NC₆H₄ 623 Me₂NCH₂ 4-pyridyl 624 Me₂NCH₂ 3-pyridyl 625 Me₂NCH₂ 2-pyridyl 626 Me₂NCH₂ 2-thiazolyl 627 Me₂NCH₂ 2-pyrazolyl 628 Me₂NCH₂ 5-isoquinolyl 629 Me₂NCH₂ 3,4- methylenedioxyC₆H₃ 630 Me₂NCH₂ 3,4- ethylenedioxyC₆H₃ 631 Me₂NCH₂ 2-imidazolyl 632 Me₂NCH₂ 2-oxazolyl 633 Me₂NCH₂ 4-isoxazolyl 634 Me₂NCH₂ 4-HOC₆H₄ 635 Me₂NCH₂ 3-HOC₆H₄ 636 Me₂NCH₂ 3,4-diHOC₆H₄ 637 Me₂NCH₂ 4-NH₂CH₂C₆H₄ 638 Me₂NCH₂ 3-NH₂CH₂C₆H₄ 639 EtNHCH₂ 3-MeOC₆H₄ 640 EtNHCH₂ 4-NH₂C₆H₄ 641 EtNHCH₂ 3-NH₂C₆H₄ 642 EtNHCH₂ 2-NH₂C₆H₄ 643 EtNHCH₂ 4-Me₂NC₆H₄ 644 EtNHCH₂ 3-Me₂NC₆H₄ 645 EtNHCH₂ 2-Me₂NC₆H₄ 646 EtNHCH₂ 4-pyridyl 647 EtNHCH₂ 3-pyridyl 648 EtNHCH₂ 2-pyridyl 649 EtNHCH₂ 2-thiazolyl 650 EtNHCH₂ 2-pyrazolyl 651 EtNHCH₂ 5-isoquinolyl 652 EtNHCH₂ 3,4- methylenedioxyC₆H₃ 653 EtNHCH₂ 3,4- ethylenedioxyC₆H₃ 654 EtNHCH₂ 2-imidazolyl 655 EtNHCH₂ 2-oxazolyl 656 EtNHCH₂ 4-isoxazolyl 657 EtNHCH₂ 4-HOC₆H₄ 658 EtNHCH₂ 3-HOC₆H₄ 659 EtNHCH₂ 3,4-diHOC₆H₄ 660 EtNHCH₂ 4-NH₂CH₂C₆H₄ 661 EtNHCH₂ 3-NH₂CH₂C₆H₄ 662 HOCH₂CH₂NHCH₂ 3-MeOC₆H₄ 663 HOCH₂CH₂NHCH₂ 4-NH₂C₆H₄ 664 HOCH₂CH₂NHCH₂ 3-NH₂C₆H₄ 665 HOCH₂CH₂NHCH₂ 2-NH₂C₆H₄ 666 HOCH₂CH₂NHCH₂ 4-Me₂NC₆H₄ 667 HOCH₂CH₂NHCH₂ 3-Me₂NC₆H₄ 668 HOCH₂CH₂NHCH₂ 2-Me₂NC₆H₄ 669 HOCH₂CH₂NHCH₂ 4-pyridyl 670 HOCH₂CH₂NHCH₂ 3-pyridyl 671 HOCH₂CH₂NHCH₂ 2-pyridyl 672 HOCH₂CH₂NHCH₂ 2-thiazolyl 673 HOCH₂CH₂NHCH₂ 2-pyrazolyl 674 HOCH₂CH₂NHCH₂ 5-isoquinolyl 675 HOCH₂CH₂NHCH₂ 3,4- methylenedioxyC₆H₃ 676 HOCH₂CH₂NHCH₂ 3,4- ethylenedioxyC₆H₃ 677 HOCH₂CH₂NHCH₂ 2-imidazolyl 678 HOCH₂CH₂NHCH₂ 2-oxazolyl 679 HOCH₂CH₂NHCH₂ 4-isoxazolyl 680 HOCH₂CH₂NHCH₂ 4-HOC₆H₄ 681 HOCH₂CH₂NHCH₂ 3-HOC₆H₄ 682 HOCH₂CH₂NHCH₂ 3,4-diHOC₆H₄ 683 HOCH₂CH₂NHCH₂ 4-NH₂CH₂C₆H₄ 684 HOCH₂CH₂NHCH₂ 3-NH₂CH₂C₆H₄ 685 H₂NCH₂CH₂NHCH₂ 4-MeOC₆H₄ 686 H₂NCH₂CH₂NHCH₂ 3-MeOC₆H₄ 687 H₂NCH₂CH₂NHCH₂ 4-NH₂C₆H₄ 688 H₂NCH₂CH₂NHCH₂ 3-NH₂C₆H₄ 689 H₂NCH₂CH₂NHCH₂ 2-NH₂C₆H₄ 690 H₂NCH₂CH₂NHCH₂ 4-Me₂NC₆H₄ 691 H₂NCH₂CH₂NHCH₂ 3-Me₂NC₆H₄ 692 H₂NCH₂CH₂NHCH₂ 2-Me₂NC₆H₄ 693 H₂NCH₂CH₂NHCH₂ 4-pyridyl 694 H₂NCH₂CH₂NHCH₂ 3-pyridyl 695 H₂NCH₂CH₂NHCH₂ 2-pyridyl 696 H₂NCH₂CH₂NHCH₂ 2-thiazolyl 697 H₂NCH₂CH₂NHCH₂ 2-pyrazolyl 698 H₂NCH₂CH₂NHCH₂ 5-isoquinolyl 699 H₂NCH₂CH₂NHCH₂ 3,4- methylenedioxyC₆H₃ 700 H₂NCH₂CH₂NHCH₂ 3,4- ethylenedioxyC₆H₃ 701 H₂NCH₂CH₂NHCH₂ 2-imidazolyl 702 H₂NCH₂CH₂NHCH₂ 2-oxazolyl 703 H₂NCH₂CH₂NHCH₂ 4-isoxazolyl 704 H₂NCH₂CH₂NHCH₂ 4-HOC₆H₄ 705 H₂NCH₂CH₂NHCH₂ 3-HOC₆H₄ 706 H₂NCH₂CH₂NHCH₂ 3,4-diHOC₆H₄ 707 H₂NCH₂CH₂NHCH₂ 4-NH₂CH₂C₆H₄ 708 H₂NCH₂CH₂NHCH₂ 3-NH₂CH₂C₆H₄ 709 Me₂NCH₂CH₂NHCH₂ 4-MeOC₆H₄ 710 Me₂NCH₂CH₂NHCH₂ 3-MeOC₆H₄ 711 Me₂NCH₂CH₂NHCH₂ 4-NH₂C₆H₄ 712 Me₂NCH₂CH₂NHCH₂ 3-NH₂C₆H₄ 713 Me₂NCH₂CH₂NHCH₂ 2-NH₂C₆H₄ 714 Me₂NCH₂CH₂NHCH₂ 4-Me₂NC₆H₄ 715 Me₂NCH₂CH₂NHCH₂ 3-Me₂NC₆H₄ 716 Me₂NCH₂CH₂NHCH₂ 2-Me₂NC₆H₄ 717 Me₂NCH₂CH₂NHCH₂ 4-pyridyl 718 Me₂NCH₂CH₂NHCH₂ 3-pyridyl 719 Me₂NCH₂CH₂NHCH₂ 2-pyridyl 720 Me₂NCH₂CH₂NHCH₂ 2-thiazolyl 721 Me₂NCH₂CH₂NHCH₂ 2-pyrazolyl 722 Me₂NCH₂CH₂NHCH₂ 5-isoquinolyl 723 Me₂NCH₂CH₂NHCH₂ 3,4- methylenedioxyC₆H₃ 724 Me₂NCH₂CH₂NHCH₂ 3,4- ethylenedioxyC₆H₃ 725 Me₂NCH₂CH₂NHCH₂ 2-imidazolyl 726 Me₂NCH₂CH₂NHCH₂ 2-oxazolyl 727 Me₂NCH₂CH₂NHCH₂ 4-isoxazolyl 728 Me₂NCH₂CH₂NHCH₂ 4-HOC₆H₄ 729 Me₂NCH₂CH₂NHCH₂ 3-HOC₆H₄ 730 Me₂NCH₂CH₂NHCH₂ 3,4-diHOC₆H₄ 731 Me₂NCH₂CH₂NHCH₂ 4-NH₂CH₂C₆H₄ 732 Me₂NCH₂CH₂NHCH₂ 3-NH₂CH₂C₆H₄ 733 1-morpholinylmethyl 3-MeOC₆H₄ 734 1-morpholinylmethyl 4-NH₂C₆H₄ 735 1-morpholinylmethyl 3-NH₂C₆H₄ 736 1-morpholinylmethyl 2-NH₂C₆H₄ 737 1-morpholinylmethyl 4-Me₂NC₆H₄ 738 1-morpholinylmethyl 3-Me₂NC₆H₄ 739 1-morpholinylmethyl 2-Me₂NC₆H₄ 740 1-morpholinylmethyl 4-pyridyl 741 1-morpholinylmethyl 3-pyridyl 742 1-morpholinylmethyl 2-pyridyl 743 1-morpholinylmethyl 2-thiazolyl 744 1-morpholinylmethyl 2-pyrazolyl 745 1-morpholinylmethyl 5-isoquinolyl 746 1-morpholinylmethyl 3,4- methylenedioxyC₆H₃ 747 1-morpholinylmethyl 3,4- ethylenedioxyC₆H₃ 748 1-morpholinylmethyl 2-imidazolyl 749 1-morpholinylmethyl 2-oxazolyl 750 1-morpholinylmethyl 4-isoxazolyl 751 1-morpholinylmethyl 4-HOC₆H₄ 752 1-morpholinylmethyl 3-HOC₆H₄ 753 1-morpholinylmethyl 3,4-diHOC₆H₄ 754 1-morpholinylmethyl 4-NH₂CH₂C₆H₄ 755 1-morpholinylmethyl 3-NH₂CH₂C₆H₄ 756 1-thiomorpholinylmethyl 3-MeOC₆H₄ 757 1-thiomorpholinylmethyl 4-NH₂C₆H₄ 758 1-thiomorpholinylmethyl 3-NH₂C₆H₄ 759 1-thiomorpholinylmethyl 2-NH₂C₆H₄ 760 1-thiomorpholinylmethyl 4-Me₂NC₆H₄ 761 1-thiomorpholinylmethyl 3-Me₂NC₆H₄ 762 1-thiomorpholinylmethyl 2-Me₂NC₆H₄ 763 1-thiomorpholinylmethyl 4-pyridyl 764 1-thiomorpholinylmethyl 3-pyridyl 765 1-thiomorpholinylmethyl 2-pyridyl 766 1-thiomorpholinylmethyl 2-thiazolyl 767 1-thiomorpholinylmethyl 2-pyrazolyl 768 1-thiomorpholinylmethyl 5-isoquinolyl 769 1-thiomorpholinylmethyl 3,4- methylenedioxyC₆H₃ 770 1-thiomorpholinylmethyl 3,4- ethylenedioxyC₆H₃ 771 1-thiomorpholinylmethyl 2-imidazolyl 772 1-thiomorpholinylmethyl 2-oxazolyl 773 1-thiomorpholinylmethyl 4-isoxazolyl 774 1-thiomorpholinylmethyl 4-HOC₆H₄ 775 1-thiomorpholinylmethyl 3-HOC₆H₄ 776 1-thiomorpholinylmethyl 3,4-diHOC₆H₄ 777 1-thiomorpholinylmethyl 4-NH₂CH₂C₆H₄ 778 1-thiomorpholinylmethyl 3-NH₂CH₂C₆H₄ 779 1-piperazinylmethyl 3-MeOC₆H₄ 780 1-piperazinylmethyl 4-NH₂C₆H₄ 781 1-piperazinylmethyl 3-NH₂C₆H₄ 782 1-piperazinylmethyl 2-NH₂C₆H₄ 783 1-piperazinylmethyl 4-Me₂NC₆H₄ 784 1-piperazinylmethyl 3-Me₂NC₆H₄ 785 1-piperazinylmethyl 2-Me₂NC₆H₄ 786 1-piperazinylmethyl 4-pyridyl 787 1-piperazinylmethyl 3-pyridyl 788 1-piperazinylmethyl 2-pyridyl 789 1-piperazinylmethyl 2-thiazolyl 790 1-piperazinylmethyl 2-pyrazolyl 791 1-piperazinylmethyl 5-isoquinolyl 792 1-piperazinylmethyl 3,4- methylenedioxyC₆H₃ 793 1-piperazinylmethyl 3,4- ethylenedioxyC₆H₃ 794 1-piperazinylmethyl 2-imidazolyl 795 1-piperazinylmethyl 2-oxazolyl 796 1-piperazinylmethyl 4-isoxazolyl 797 1-piperazinylmethyl 4-HOC₆H₄ 798 1-piperazinylmethyl 3-HOC₆H₄ 799 1-piperazinylmethyl 3,4-diHOC₆H₄ 800 1-piperazinylmethyl 4-NH₂CH₂C₆H₄ 801 1-piperazinylmethyl 3-NH₂CH₂C₆H₄

TABLE 3

Example Number R¹ R² 802 2-pyridylmethyl 4-MeOC₆H₄ 803 2-pyridylmethyl 3-MeOC₆H₄ 804 2-pyridylmethyl 4-NH₂C₆H₄ 805 2-pyridylmethyl 3-NH₂C₆H₄ 806 2-pyridylmethyl 2-NH₂C₆H₄ 807 2-pyridylmethyl 4-Me₂NC₆H₄ 808 2-pyridylmethyl 3-Me₂NC₆H₄ 809 2-pyridylmethyl 2-Me₂NC₆H₄ 810 2-pyridylmethyl 4-pyridyl 811 2-pyridylmethyl 3-pyridyl 812 2-pyridylmethyl 2-pyridyl 813 2-pyridylmethyl 2-thiazolyl 814 2-pyridylmethyl 2-pyrazolyl 815 2-pyridylmethyl 5-isoquinolyl 816 2-pyridylmethyl 3,4- methylenedioxyC₆H₃ 817 2-pyridylmethyl 3,4- ethylenedioxyC₆H₃ 818 2-pyridylmethyl 2-imidazolyl 819 2-pyridylmethyl 2-oxazolyl 820 2-pyridylmethyl 4-isoxazolyl 821 2-pyridylmethyl 4-HOC₆H₄ 822 2-pyridylmethyl 3-HOC₆H₄ 823 2-pyridylmethyl 3,4-diHOC₆H₄ 824 2-pyridylmethyl 4-NH₂CH₂C₆H₄ 825 2-pyridylmethyl 3-NH₂CH₂C₆H₄ 826 3-pyridylmethyl 4-MeOC₆H₄ 827 3-pyridylmethyl 3-MeOC₆H₄ 828 3-pyridylmethyl 4-NH₂C₆H₄ 829 3-pyridylmethyl 3-NH₂C₆H₄ 830 3-pyridylmethyl 2-NH₂C₆H₄ 831 3-pyridylmethyl 4-Me₂NC₆H₄ 832 3-pyridylmethyl 3-Me₂NC₆H₄ 833 3-pyridylmethyl 2-Me₂NC₆H₄ 834 3-pyridylmethyl 4-pyridyl 835 3-pyridylmethyl 3-pyridyl 836 3-pyridylmethyl 2-pyridyl 837 3-pyridylmethyl 2-thiazolyl 838 3-pyridylmethyl 2-pyrazolyl 839 3-pyridylmethyl 5-isoquinolyl 840 3-pyridylmethyl 3,4- methylenedioxyC₆H₃ 841 3-pyridylmethyl 3,4- ethylenedioxyC₆H₃ 842 3-pyridylmethyl 2-imidazolyl 843 3-pyridylmethyl 2-oxazolyl 844 3-pyridylmethyl 4-isoxazolyl 845 3-pyridylmethyl 4-HOC₆H₄ 846 3-pyridylmethyl 3-HOC₆H₄ 847 3-pyridylmethyl 3,4-diHOC₆H₄ 848 3-pyridylmethyl 4-NH₂CH₂C₆H₄ 849 3-pyridylmethyl 3-NH₂CH₂C₆H₄ 850 4-pyridylmethyl 4-MeOC₆H₄ 851 4-pyridylmethyl 3-MeOC₆H₄ 852 4-pyridylmethyl 4-NH₂C₆H₄ 853 4-pyridylmethyl 3-NH₂C₆H₄ 854 4-pyridylmethyl 2-NH₂C₆H₄ 855 4-pyridylmethyl 4-Me₂NC₆H₄ 856 4-pyridylmethyl 3-Me₂NC₆H₄ 857 4-pyridylmethyl 2-Me₂NC₆H₄ 858 4-pyridylmethyl 4-pyridyl 859 4-pyridylmethyl 3-pyridyl 860 4-pyridylmethyl 2-pyridyl 861 4-pyridylmethyl 2-thiazolyl 862 4-pyridylmethyl 2-pyrazolyl 863 4-pyridylmethyl 5-isoquinolyl 864 4-pyridylmethyl 3,4- methylenedioxyC₆H₃ 865 4-pyridylmethyl 3,4- ethylenedioxyC₆H₃ 866 4-pyridylmethyl 2-imidazolyl 867 4-pyridylmethyl 2-oxazolyl 868 4-pyridylmethyl 4-isoxazolyl 869 4-pyridylmethyl 4-HOC₆H₄ 870 4-pyridylmethyl 3-HOC₆H₄ 871 4-pyridylmethyl 3,4-diHOC₆H₄ 872 4-pyridylmethyl 4-NH₂CH₂C₆H₄ 873 4-pyridylmethyl 3-NH₂CH₂C₆H₄ 874 2-NH₂C₆H₄ 4-MeOC₆H₄ 875 2-NH₂C₆H₄ 3-MeOC₆H₄ 876 2-NH₂C₆H₄ 4-NH₂C₆H₄ 877 2-NH₂C₆H₄ 3-NH₂C₆H₄ 878 2-NH₂C₆H₄ 2-NH₂C₆H₄ 879 2-NH₂C₆H₄ 4-Me₂NC₆H₄ 880 2-NH₂C₆H₄ 3-Me₂NC₆H₄ 881 2-NH₂C₆H₄ 2-Me₂NC₆H₄ 882 2-NH₂C₆H₄ 4-pyridyl 883 2-NH₂C₆H₄ 3-pyridyl 884 2-NH₂C₆H₄ 2-pyridyl 885 2-NH₂C₆H₄ 2-thiazolyl 886 2-NH₂C₆H₄ 2-pyrazolyl 887 2-NH₂C₆H₄ 5-isoquinolyl 888 2-NH₂C₆H₄ 3,4- methylenedioxyC₆H₃ 889 2-NH₂C₆H₄ 3,4- ethylenedioxyC₆H₃ 890 2-NH₂C₆H₄ 2-imidazolyl 891 2-NH₂C₆H₄ 2-oxazolyl 892 2-NH₂C₆H₄ 4-isoxazolyl 893 2-NH₂C₆H₄ 4-HOC₆H₄ 894 2-NH₂C₆H₄ 3-HOC₆H₄ 895 2-NH₂C₆H₄ 3,4-diHOC₆H₄ 896 2-NH₂C₆H₄ 4-NH₂CH₂C₆H₄ 897 2-NH₂C₆H₄ 3-NH₂CH₂C₆H₄ 898 3-NH₂C₆H₄ 4-MeOC₆H₄ 899 3-NH₂C₆H₄ 3-MeOC₆H₄ 900 3-NH₂C₆H₄ 4-NH₂C₆H₄ 901 3-NH₂C₆H₄ 3-NH₂C₆H₄ 902 3-NH₂C₆H₄ 2-NH₂C₆H₄ 903 3-NH₂C₆H₄ 4-Me₂NC₆H₄ 904 3-NH₂C₆H₄ 3-Me₂NC₆H₄ 905 3-NH₂C₆H₄ 2-Me₂NC₆H₄ 906 3-NH₂C₆H₄ 4-pyridyl 907 3-NH₂C₆H₄ 3-pyridyl 908 3-NH₂C₆H₄ 2-pyridyl 909 3-NH₂C₆H₄ 2-thiazolyl 910 3-NH₂C₆H₄ 2-pyrazolyl 911 3-NH₂C₆H₄ 5-isoquinolyl 912 3-NH₂C₆H₄ 3,4- methylenedioxyC₆H₃ 913 3-NH₂C₆H₄ 3,4- ethylenedioxyC₆H₃ 914 3-NH₂C₆H₄ 2-imidazolyl 915 3-NH₂C₆H₄ 2-oxazolyl 916 3-NH₂C₆H₄ 4-isoxazolyl 917 3-NH₂C₆H₄ 4-HOC₆H₄ 918 3-NH₂C₆H₄ 3-HOC₆H₄ 919 3-NH₂C₆H₄ 3,4-diHOC₆H₄ 920 3-NH₂C₆H₄ 4-NH₂CH₂C₆H₄ 921 3-NH₂C₆H₄ 3-NH₂CH₂C₆H₄ 922 4-NH₂C₆H₄ 4-MeOC₆H₄ 923 4-NH₂C₆H₄ 3-MeOC₆H₄ 924 4-NH₂C₆H₄ 4-NH₂C₆H₄ 925 4-NH₂C₆H₄ 3-NH₂C₆H₄ 926 4-NH₂C₆H₄ 2-NH₂C₆H₄ 927 4-NH₂C₆H₄ 4-Me₂NC₆H₄ 928 4-NH₂C₆H₄ 3-Me₂NC₆H₄ 930 4-NH₂C₆H₄ 2-Me₂NC₆H₄ 931 4-NH₂C₆H₄ 4-pyridyl 932 4-NH₂C₆H₄ 3-pyridyl 933 4-NH₂C₆H₄ 2-pyridyl 934 4-NH₂C₆H₄ 2-thiazolyl 935 4-NH₂C₆H₄ 2-pyrazolyl 936 4-NH₂C₆H₄ 5-isoquinolyl 937 4-NH₂C₆H₄ 3,4- methylenedioxyC₆H₃ 938 4-NH₂C₆H₄ 3,4- ethylenedioxyC₆H₃ 939 4-NH₂C₆H₄ 2-imidazolyl 940 4-NH₂C₆H₄ 2-oxazolyl 941 4-NH₂C₆H₄ 4-isoxazolyl 942 4-NH₂C₆H₄ 4-HOC₆H₄ 943 4-NH₂C₆H₄ 3-HOC₆H₄ 944 4-NH₂C₆H₄ 3,4-diHOC₆H₄ 945 4-NH₂C₆H₄ 4-NH₂CH₂C₆H₄ 946 4-NH₂C₆H₄ 3-NH₂CH₂C₆H₄ 947 2-MeOC₆H₄ 4-MeOC₆H₄ 948 2-MeOC₆H₄ 3-MeOC₆H₄ 949 2-MeOC₆H₄ 4-NH₂C₆H₄ 950 2-MeOC₆H₄ 3-NH₂C₆H₄ 951 2-MeOC₆H₄ 2-NH₂C₆H₄ 952 2-MeOC₆H₄ 4-Me₂NC₆H₄ 953 2-MeOC₆H₄ 3-Me₂NC₆H₄ 954 2-MeOC₆H₄ 2-Me₂NC₆H₄ 955 2-MeOC₆H₄ 4-pyridyl 956 2-MeOC₆H₄ 3-pyridyl 957 2-MeOC₆H₄ 2-pyridyl 958 2-MeOC₆H₄ 2-thiazolyl 959 2-MeOC₆H₄ 2-pyrazolyl 960 2-MeOC₆H₄ 5-isoquinolyl 961 2-MeOC₆H₄ 3,4- methylenedioxyC₆H₃ 962 2-MeOC₆H₄ 3,4- ethylenedioxyC₆H₃ 963 2-MeOC₆H₄ 2-imidazolyl 964 2-MeOC₆H₄ 2-oxazolyl 965 2-MeOC₆H₄ 4-isoxazolyl 966 2-MeOC₆H₄ 4-HOC₆H₄ 967 2-MeOC₆H₄ 3-HOC₆H₄ 968 2-MeOC₆H₄ 3,4-diHOC₆H₄ 969 2-MeOC₆H₄ 4-NH₂CH₂C₆H₄ 970 2-MeOC₆H₄ 3-NH₂CH₂C₆H₄ 971 3-MeOC₆H₄ 4-MeOC₆H₄ 972 3-MeOC₆H₄ 3-MeOC₆H₄ 973 3-MeOC₆H₄ 4-NH₂C₆H₄ 974 3-MeOC₆H₄ 3-NH₂C₆H₄ 975 3-MeOC₆H₄ 2-NH₂C₆H₄ 976 3-MeOC₆H₄ 4-Me₂NC₆H₄ 977 3-MeOC₆H₄ 3-Me₂NC₆H₄ 978 3-MeOC₆H₄ 2-Me₂NC₆H₄ 979 3-MeOC₆H₄ 4-pyridyl 980 3-MeOC₆H₄ 3-pyridyl 981 3-MeOC₆H₄ 2-pyridyl 982 3-MeOC₆H₄ 2-thiazolyl 983 3-MeOC₆H₄ 2-pyrazolyl 984 3-MeOC₆H₄ 5-isoquinolyl 985 3-MeOC₆H₄ 3,4- methylenedioxyC₆H₃ 986 3-MeOC₆H₄ 3,4- ethylenedioxyC₆H₃ 987 3-MeOC₆H₄ 2-imidazolyl 988 3-MeOC₆H₄ 2-oxazolyl 989 3-MeOC₆H₄ 4-isoxazolyl 990 3-MeOC₆H₄ 4-HOC₆H₄ 991 3-MeOC₆H₄ 3-HOC₆H₄ 992 3-MeOC₆H₄ 3,4-diHOC₆H₄ 993 3-MeOC₆H₄ 4-NH₂CH₂C₆H₄ 994 3-MeOC₆H₄ 3-NH₂CH₂C₆H₄ 995 4-MeOC₆H₄ 4-MeOC₆H₄ 996 4-MeOC₆H₄ 3-MeOC₆H₄ 997 4-MeOC₆H₄ 4-NH₂C₆H₄ 998 4-MeOC₆H₄ 3-NH₂C₆H₄ 999 4-MeOC₆H₄ 2-NH₂C₆H₄ 1000 4-MeOC₆H₄ 4-Me₂NC₆H₄ 1001 4-MeOC₆H₄ 3-Me₂NC₆H₄ 1002 4-MeOC₆H₄ 2-Me₂NC₆H₄ 1003 4-MeOC₆H₄ 4-pyridyl 1004 4-MeOC₆H₄ 3-pyridyl 1005 4-MeOC₆H₄ 2-pyridyl 1006 4-MeOC₆H₄ 2-thiazolyl 1007 4-MeOC₆H₄ 2-pyrazolyl 1008 4-MeOC₆H₄ 5-isoquinolyl 1009 4-MeOC₆H₄ 3,4- methylenedioxyC₆H₃ 1010 4-MeOC₆H₄ 3,4- ethylenedioxyC₆H₃ 1011 4-MeOC₆H₄ 2-imidazolyl 1012 4-MeOC₆H₄ 2-oxazolyl 1013 4-MeOC₆H₄ 4-isoxazolyl 1014 4-MeOC₆H₄ 4-HOC₆H₄ 1015 4-MeOC₆H₄ 3-HOC₆H₄ 1016 4-MeOC₆H₄ 3,4-diHOC₆H₄ 1017 4-MeOC₆H₄ 4-NH₂CH₂C₆H₄ 1018 4-MeOC₆H₄ 3-NH₂CH₂C₆H₄ 1019 2-HOC₆H₄ 4-MeOC₆H₄ 1020 2-HOC₆H₄ 3-MeOC₆H₄ 1021 2-HOC₆H₄ 4-NH₂C₆H₄ 1022 2-HOC₆H₄ 3-NH₂C₆H₄ 1023 2-HOC₆H₄ 2-NH₂C₆H₄ 1024 2-HOC₆H₄ 4-Me₂NC₆H₄ 1025 2-HOC₆H₄ 3-Me₂NC₆H₄ 1026 2-HOC₆H₄ 2-Me₂NC₆H₄ 1027 2-HOC₆H₄ 4-pyridyl 1028 2-HOC₆H₄ 3-pyridyl 1029 2-HOC₆H₄ 2-pyridyl 1030 2-HOC₆H₄ 2-thiazolyl 1031 2-HOC₆H₄ 2-pyrazolyl 1032 2-HOC₆H₄ 5-isoquinolyl 1033 2-HOC₆H₄ 3,4- methylenedioxyC₆H₃ 1034 2-HOC₆H₄ 3,4- ethylenedioxyC₆H₃ 1035 2-HOC₆H₄ 2-imidazolyl 1036 2-HOC₆H₄ 2-oxazolyl 1037 2-HOC₆H₄ 4-isoxazolyl 1038 2-HOC₆H₄ 4-HOC₆H₄ 1039 2-HOC₆H₄ 3-HOC₆H₄ 1040 2-HOC₆H₄ 3,4-diHOC₆H₄ 1041 2-HOC₆H₄ 4-NH₂CH₂C₆H₄ 1042 2-HOC₆H₄ 3-NH₂CH₂C₆H₄ 1043 3-HOC₆H₄ 4-MeOC₆H₄ 1044 3-HOC₆H₄ 3-MeOC₆H₄ 1045 3-HOC₆H₄ 4-NH₂C₆H₄ 1046 3-HOC₆H₄ 3-NH₂C₆H₄ 1047 3-HOC₆H₄ 2-NH₂C₆H₄ 1048 3-HOC₆H₄ 4-Me₂NC₆H₄ 1049 3-HOC₆H₄ 3-Me₂NC₆H₄ 1050 3-HOC₆H₄ 2-Me₂NC₆H₄ 1051 3-HOC₆H₄ 4-pyridyl 1052 3-HOC₆H₄ 3-pyridyl 1053 3-HOC₆H₄ 2-pyridyl 1054 3-HOC₆H₄ 2-thiazolyl 1055 3-HOC₆H₄ 2-pyrazolyl 1056 3-HOC₆H₄ 5-isoquinolyl 1057 3-HOC₆H₄ 3,4- methylenedioxyC₆H₃ 1058 3-HOC₆H₄ 3,4- ethylenedioxyC₆H₃ 1059 3-HOC₆H₄ 2-imidazolyl 1060 3-HOC₆H₄ 2-oxazolyl 1061 3-HOC₆H₄ 4-isoxazolyl 1062 3-HOC₆H₄ 4-HOC₆H₄ 1063 3-HOC₆H₄ 3-HOC₆H₄ 1064 3-HOC₆H₄ 3,4-diHOC₆H₄ 1065 3-HOC₆H₄ 4-NH₂CH₂C₆H₄ 1066 3-HOC₆H₄ 3-NH₂CH₂C₆H₄ 1067 4-HOC₆H₄ 4-MeOC₆H₄ 1068 4-HOC₆H₄ 3-MeOC₆H₄ 1069 4-HOC₆H₄ 4-NH₂C₆H₄ 1070 4-HOC₆H₄ 3-NH₂C₆H₄ 1071 4-HOC₆H₄ 2-NH₂C₆H₄ 1072 4-HOC₆H₄ 4-Me₂NC₆H₄ 1073 4-HOC₆H₄ 3-Me₂NC₆H₄ 1074 4-HOC₆H₄ 2-Me₂NC₆H₄ 1075 4-HOC₆H₄ 4-pyridyl 1076 4-HOC₆H₄ 3-pyridyl 1077 4-HOC₆H₄ 2-pyridyl 1078 4-HOC₆H₄ 2-thiazolyl 1079 4-HOC₆H₄ 2-pyrazolyl 1080 4-HOC₆H₄ 5-isoquinolyl 1081 4-HOC₆H₄ 3,4- methylenedioxyC₆H₃ 1082 4-HOC₆H₄ 3,4- ethylenedioxyC₆H₃ 1083 4-HOC₆H₄ 2-imidazolyl 1084 4-HOC₆H₄ 2-oxazolyl 1085 4-HOC₆H₄ 4-isoxazolyl 1086 4-HOC₆H₄ 4-HOC₆H₄ 1087 4-HOC₆H₄ 3-HOC₆H₄ 1088 4-HOC₆H₄ 3,4-diHOC₆H₄ 1089 4-HOC₆H₄ 4-NH₂CH₂C₆H₄ 1090 4-HOC₆H₄ 3-NH₂CH₂C₆H₄ 1091 4-ClC₆H₄ 4-MeOC₆H₄ 1092 4-ClC₆H₄ 3-MeOC₆H₄ 1093 4-ClC₆H₄ 4-NH₂C₆H₄ 1094 4-ClC₆H₄ 3-NH₂C₆H₄ 1095 4-ClC₆H₄ 2-NH₂C₆H₄ 1096 4-ClC₆H₄ 4-Me₂NC₆H₄ 1097 4-ClC₆H₄ 3-Me₂NC₆H₄ 1098 4-ClC₆H₄ 2-Me₂NC₆H₄ 1099 4-ClC₆H₄ 4-pyridyl 1100 4-ClC₆H₄ 3-pyridyl 1101 4-ClC₆H₄ 2-pyridyl 1102 4-ClC₆H₄ 2-thiazolyl 1103 4-ClC₆H₄ 2-pyrazolyl 1104 4-ClC₆H₄ 5-isoquinolyl 1105 4-ClC₆H₄ 3,4- methylenedioxyC₆H₃ 1106 4-ClC₆H₄ 3,4- ethylenedioxyC₆H₃ 1107 4-ClC₆H₄ 2-imidazolyl 1108 4-ClC₆H₄ 2-oxazolyl 1109 4-ClC₆H₄ 4-isoxazolyl 1110 4-ClC₆H₄ 4-HOC₆H₄ 1111 4-ClC₆H₄ 3-HOC₆H₄ 1112 4-ClC₆H₄ 3,4-diHOC₆H₄ 1113 4-ClC₆H₄ 4-NH₂CH₂C₆H₄ 1114 4-ClC₆H₄ 3-NH₂CH₂C₆H₄ 1115 2-NH₂CH₂C₆H₄ 4-MeOC₆H₄ 1116 2-NH₂CH₂C₆H₄ 3-MeOC₆H₄ 1117 2-NH₂CH₂C₆H₄ 4-NH₂C₆H₄ 1118 2-NH₂CH₂C₆H₄ 3-NH₂C₆H₄ 1119 2-NH₂CH₂C₆H₄ 2-NH₂C₆H₄ 1120 2-NH₂CH₂C₆H₄ 4-Me₂NC₆H₄ 1121 2-NH₂CH₂C₆H₄ 3-Me₂NC₆H₄ 1122 2-NH₂CH₂C₆H₄ 2-Me₂NC₆H₄ 1123 2-NH₂CH₂C₆H₄ 4-pyridyl 1124 2-NH₂CH₂C₆H₄ 3-pyridyl 1125 2-NH₂CH₂C₆H₄ 2-pyridyl 1126 2-NH₂CH₂C₆H₄ 2-thiazolyl 1127 2-NH₂CH₂C₆H₄ 2-pyrazolyl 1128 2-NH₂CH₂C₆H₄ 5-isoquinolyl 1129 2-NH₂CH₂C₆H₄ 3,4- methylenedioxyC₆H₃ 1130 2-NH₂CH₂C₆H₄ 3,4- ethylenedioxyC₆H₃ 1131 2-NH₂CH₂C₆H₄ 2-imidazolyl 1132 2-NH₂CH₂C₆H₄ 2-oxazolyl 1133 2-NH₂CH₂C₆H₄ 4-isoxazolyl 1134 2-NH₂CH₂C₆H₄ 4-HOC₆H₄ 1135 2-NH₂CH₂C₆H₄ 3-HOC₆H₄ 1136 2-NH₂CH₂C₆H₄ 3,4-diHOC₆H₄ 1137 2-NH₂CH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1138 2-NH₂CH₂C₆H₄ 3-NH₂CH₂C₆H₄ 1139 3-NH₂CH₂C₆H₄ 4-MeOC₆H₄ 1140 3-NH₂CH₂C₆H₄ 3-MeOC₆H₄ 1141 3-NH₂CH₂C₆H₄ 4-NH₂C₆H₄ 1142 3-NH₂CH₂C₆H₄ 3-NH₂C₆H₄ 1143 3-NH₂CH₂C₆H₄ 2-NH₂C₆H₄ 1144 3-NH₂CH₂C₆H₄ 4-Me₂NC₆H₄ 1145 3-NH₂CH₂C₆H₄ 3-Me₂NC₆H₄ 1146 3-NH₂CH₂C₆H₄ 2-Me₂NC₆H₄ 1147 3-NH₂CH₂C₆H₄ 4-pyridyl 1148 3-NH₂CH₂C₆H₄ 3-pyridyl 1149 3-NH₂CH₂C₆H₄ 2-pyridyl 1150 3-NH₂CH₂C₆H₄ 2-thiazolyl 1151 3-NH₂CH₂C₆H₄ 2-pyrazolyl 1152 3-NH₂CH₂C₆H₄ 5-isoquinolyl 1153 3-NH₂CH₂C₆H₄ 3,4- methylenedioxyC₆H₃ 1154 3-NH₂CH₂C₆H₄ 3,4- ethylenedioxyC₆H₃ 1155 3-NH₂CH₂C₆H₄ 2-imidazolyl 1156 3-NH₂CH₂C₆H₄ 2-oxazolyl 1157 3-NH₂CH₂C₆H₄ 4-isoxazolyl 1158 3-NH₂CH₂C₆H₄ 4-HOC₆H₄ 1159 3-NH₂CH₂C₆H₄ 3-HOC₆H₄ 1160 3-NH₂CH₂C₆H₄ 3,4-diHOC₆H₄ 1161 3-NH₂CH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1162 3-NH₂CH₂C₆H₄ 3-NH₂CH₂C₆H₄ 1163 4-NH₂CH₂C₆H₄ 4-MeOC₆H₄ 1164 4-NH₂CH₂C₆H₄ 3-MeOC₆H₄ 1165 4-NH₂CH₂C₆H₄ 4-NH₂C₆H₄ 1166 4-NH₂CH₂C₆H₄ 3-NH₂C₆H₄ 1167 4-NH₂CH₂C₆H₄ 2-NH₂C₆H₄ 1168 4-NH₂CH₂C₆H₄ 4-Me₂NC₆H₄ 1169 4-NH₂CH₂C₆H₄ 3-Me₂NC₆H₄ 1170 4-NH₂CH₂C₆H₄ 2-Me₂NC₆H₄ 1171 4-NH₂CH₂C₆H₄ 4-pyridyl 1172 4-NH₂CH₂C₆H₄ 3-pyridyl 1173 4-NH₂CH₂C₆H₄ 2-pyridyl 1174 4-NH₂CH₂C₆H₄ 2-thiazolyl 1175 4-NH₂CH₂C₆H₄ 2-pyrazolyl 1176 4-NH₂CH₂C₆H₄ 5-isoquinolyl 1177 4-NH₂CH₂C₆H₄ 3,4- methylenedioxyC₆H₃ 1178 4-NH₂CH₂C₆H₄ 3,4- ethylenedioxyC₆H₃ 1179 4-NH₂CH₂C₆H₄ 2-imidazolyl 1180 4-NH₂CH₂C₆H₄ 2-oxazolyl 1181 4-NH₂CH₂C₆H₄ 4-isoxazolyl 1182 4-NH₂CH₂C₆H₄ 4-HOC₆H₄ 1183 4-NH₂CH₂C₆H₄ 3-HOC₆H₄ 1184 4-NH₂CH₂C₆H₄ 3,4-diHOC₆H₄ 1185 4-NH₂CH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1186 4-NH₂CH₂C₆H₄ 3-NH₂CH₂C₆H₄ 1187 2-Me₂NCH₂C₆H₄ 4-MeOC₆H₄ 1188 2-Me₂NCH₂C₆H₄ 3-MeOC₆H₄ 1189 2-Me₂NCH₂C₆H₄ 4-NH₂C₆H₄ 1190 2-Me₂NCH₂C₆H₄ 3-NH₂C₆H₄ 1191 2-Me₂NCH₂C₆H₄ 2-NH₂C₆H₄ 1192 2-Me₂NCH₂C₆H₄ 4-Me₂NC₆H₄ 1193 2-Me₂NCH₂C₆H₄ 3-Me₂NC₆H₄ 1194 2-Me₂NCH₂C₆H₄ 2-Me₂NC₆H₄ 1195 2-Me₂NCH₂C₆H₄ 4-pyridyl 1196 2-Me₂NCH₂C₆H₄ 3-pyridyl 1197 2-Me₂NCH₂C₆H₄ 2-pyridyl 1198 2-Me₂NCH₂C₆H₄ 2-thiazolyl 1199 2-Me₂NCH₂C₆H₄ 2-pyrazolyl 1200 2-Me₂NCH₂C₆H₄ 5-isoquinolyl 1201 2-Me₂NCH₂C₆H₄ 3,4- methylenedioxyC₆H₃ 1202 2-Me₂NCH₂C₆H₄ 3,4- ethylenedioxyC₆H₃ 1203 2-Me₂NCH₂C₆H₄ 2-imidazolyl 1204 2-Me₂NCH₂C₆H₄ 2-oxazolyl 1205 2-Me₂NCH₂C₆H₄ 4-isoxazolyl 1206 2-Me₂NCH₂C₆H₄ 4-HOC₆H₄ 1207 2-Me₂NCH₂C₆H₄ 3-HOC₆H₄ 1208 2-Me₂NCH₂C₆H₄ 3,4-diHOC₆H₄ 1209 2-Me₂NCH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1210 2-Me₂NCH₂C₆H₄ 3-NH₂CH₂C₆H₄ 1211 3-Me₂NCH₂C₆H₄ 4-MeOC₆H₄ 1212 3-Me₂NCH₂C₆H₄ 3-MeOC₆H₄ 1213 3-Me₂NCH₂C₆H₄ 4-NH₂C₆H₄ 1214 3-Me₂NCH₂C₆H₄ 3-NH₂C₆H₄ 1215 3-Me₂NCH₂C₆H₄ 2-NH₂C₆H₄ 1216 3-Me₂NCH₂C₆H₄ 4-Me₂NC₆H₄ 1217 3-Me₂NCH₂C₆H₄ 3-Me₂NC₆H₄ 1218 3-Me₂NCH₂C₆H₄ 2-Me₂NC₆H₄ 1219 3-Me₂NCH₂C₆H₄ 4-pyridyl 1220 3-Me₂NCH₂C₆H₄ 3-pyridyl 1221 3-Me₂NCH₂C₆H₄ 2-pyridyl 1222 3-Me₂NCH₂C₆H₄ 2-thiazolyl 1223 3-Me₂NCH₂C₆H₄ 2-pyrazolyl 1224 3-Me₂NCH₂C₆H₄ 5-isoquinolyl 1225 3-Me₂NCH₂C₆H₄ 3,4- methylenedioxyC₆H₃ 1226 3-Me₂NCH₂C₆H₄ 3,4- ethylenedioxyC₆H₃ 1227 3-Me₂NCH₂C₆H₄ 2-imidazolyl 1228 3-Me₂NCH₂C₆H₄ 2-oxazolyl 1229 3-Me₂NCH₂C₆H₄ 4-isoxazolyl 1230 3-Me₂NCH₂C₆H₄ 4-HOC₆H₄ 1231 3-Me₂NCH₂C₆H₄ 3-HOC₆H₄ 1232 3-Me₂NCH₂C₆H₄ 3,4-diHOC₆H₄ 1233 3-Me₂NCH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1234 3-Me₂NCH₂C₆H₄ 3-NH₂CH₂C₆H₄ 1235 4-Me₂NCH₂C₆H₄ 4-MeOC₆H₄ 1236 4-Me₂NCH₂C₆H₄ 3-MeOC₆H₄ 1237 4-Me₂NCH₂C₆H₄ 4-NH₂C₆H₄ 1238 4-Me₂NCH₂C₆H₄ 3-NH₂C₆H₄ 1239 4-Me₂NCH₂C₆H₄ 2-NH₂C₆H₄ 1240 4-Me₂NCH₂C₆H₄ 4-Me₂NC₆H₄ 1241 4-Me₂NCH₂C₆H₄ 3-Me₂NC₆H₄ 1242 4-Me₂NCH₂C₆H₄ 2-Me₂NC₆H₄ 1243 4-Me₂NCH₂C₆H₄ 4-pyridyl 1244 4-Me₂NCH₂C₆H₄ 3-pyridyl 1245 4-Me₂NCH₂C₆H₄ 2-pyridyl 1246 4-Me₂NCH₂C₆H₄ 2-thiazolyl 1247 4-Me₂NCH₂C₆H₄ 2-pyrazolyl 1248 4-Me₂NCH₂C₆H₄ 5-isoquinolyl 1249 4-Me₂NCH₂C₆H₄ 3,4- methylenedioxyC₆H₃ 1250 4-Me₂NCH₂C₆H₄ 3,4- ethylenedioxyC₆H₃ 1251 4-Me₂NCH₂C₆H₄ 2-imidazolyl 1252 4-Me₂NCH₂C₆H₄ 2-oxazolyl 1253 4-Me₂NCH₂C₆H₄ 4-isoxazolyl 1254 4-Me₂NCH₂C₆H₄ 4-HOC₆H₄ 1255 4-Me₂NCH₂C₆H₄ 3-HOC₆H₄ 1256 4-Me₂NCH₂C₆H₄ 3,4-diHOC₆H₄ 1257 4-Me₂NCH₂C₆H₄ 4-NH₂CH₂C₆H₄ 1258 4-Me₂NCH₂C₆H₄ 3-NH₂CH₂C₆H₄ 1259 H 4-MeOC₆H₄ 1260 H 3-MeOC₆H₄ 1261 H 4-NH₂C₆H₄ 1262 H 3-NH₂C₆H₄ 1263 H 2-NH₂C₆H₄ 1264 H 4-Me₂NC₆H₄ 1265 H 3-Me₂NC₆H₄ 1266 H 2-Me₂NC₆H₄ 1267 H 4-pyridyl 1268 H 3-pyridyl 1269 H 2-pyridyl 1270 H 2-thiazolyl 1271 H 2-pyrazolyl 1272 H 5-isoquinolyl 1273 H 3,4- methylenedioxyC₆H₃ 1274 H 3,4- ethylenedioxyC₆H₃ 1275 H 2-imidazolyl 1276 H 2-oxazolyl 1277 H 4-isoxazolyl 1278 H 4-HOC₆H₄ 1279 H 3-HOC₆H₄ 1280 H 3,4-diHOC₆H₄ 1281 H 4-NH₂CH₂C₆H₄ 1282 H 3-NH₂CH₂C₆H₄ 1283 Me 4-MeOC₆H₄ 1284 Me 3-MeOC₆H₄ 1285 Me 4-NH₂C₆H₄ 1286 Me 3-NH₂C₆H₄ 1287 Me 2-NH₂C₆H₄ 1288 Me 4-Me₂NC₆H₄ 1289 Me 3-Me₂NC₆H₄ 1290 Me 2-Me₂NC₆H₄ 1291 Me 4-pyridyl 1292 Me 3-pyridyl 1293 Me 2-pyridyl 1294 Me 2-thiazolyl 1295 Me 2-pyrazolyl 1296 Me 5-isoquinolyl 1297 Me 3,4- methylenedioxyC₆H₃ 1298 Me 3,4- ethylenedioxyC₆H₃ 1299 Me 2-imidazolyl 1300 Me 2-oxazolyl 1301 Me 4-isoxazolyl 1302 Me 4-HOC₆H₄ 1303 Me 3-HOC₆H₄ 1304 Me 3,4-diHOC₆H₄ 1305 Me 4-NH₂CH₂C₆H₄ 1306 Me 3-NH₂CH₂C₆H₄ 1307 Et 4-MeOC₆H₄ 1308 Et 3-MeOC₆H₄ 1309 Et 4-NH₂C₆H₄ 1310 Et 3-NH₂C₆H₄ 1311 Et 2-NH₂C₆H₄ 1312 Et 4-Me₂NC₆H₄ 1313 Et 3-Me₂NC₆H₄ 1314 Et 2-Me₂NC₆H₄ 1315 Et 4-pyridyl 1316 Et 3-pyridyl 1317 Et 2-pyridyl 1318 Et 2-thiazolyl 1319 Et 2-pyrazolyl 1320 Et 5-isoquinolyl 1321 Et 3,4- methylenedioxyC₆H₃ 1322 Et 3,4- ethylenedioxyC₆H₃ 1323 Et 2-imidazolyl 1324 Et 2-oxazolyl 1325 Et 4-isoxazolyl 1326 Et 4-HOC₆H₄ 1327 Et 3-HOC₆H₄ 1328 Et 3,4-diHOC₆H₄ 1329 Et 4-NH₂CH₂C₆H₄ 1330 Et 3-NH₂CH₂C₆H₄ 1331 2-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 1332 2-NH₂C₆H₄CH₂ 3-MeOC₆H₄ 1333 2-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1334 2-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1335 2-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1336 2-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1337 2-NH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1338 2-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1339 2-NH₂C₆H₄CH₂ 4-pyridyl 1340 2-NH₂C₆H₄CH₂ 3-pyridyl 1341 2-NH₂C₆H₄CH₂ 2-pyridyl 1342 2-NH₂C₆H₄CH₂ 2-thiazolyl 1343 2-NH₂C₆H₄CH₂ 2-pyrazolyl 1344 2-NH₂C₆H₄CH₂ 5-isoquinolyl 1345 2-NH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1346 2-NH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1347 2-NH₂C₆H₄CH₂ 2-imidazolyl 1348 2-NH₂C₆H₄CH₂ 2-oxazolyl 1349 2-NH₂C₆H₄CH₂ 4-isoxazolyl 1350 2-NH₂C₆H₄CH₂ 4-HOC₆H₄ 1351 2-NH₂C₆H₄CH₂ 3-HOC₆H₄ 1352 2-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1353 2-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1354 2-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1355 3-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 1356 3-NH₂C₆H₄CH₂ 3-MeOC₆H₄ 1357 3-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1358 3-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1359 3-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1360 3-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1361 3-NH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1362 3-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1363 3-NH₂C₆H₄CH₂ 4-pyridyl 1364 3-NH₂C₆H₄CH₂ 3-pyridyl 1365 3-NH₂C₆H₄CH₂ 2-pyridyl 1366 3-NH₂C₆H₄CH₂ 2-thiazolyl 1367 3-NH₂C₆H₄CH₂ 2-pyrazolyl 1367 3-NH₂C₆H₄CH₂ 5-isoquinolyl 1369 3-NH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1370 3-NH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1371 3-NH₂C₆H₄CH₂ 2-imidazolyl 1372 3-NH₂C₆H₄CH₂ 2-oxazolyl 1373 3-NH₂C₆H₄CH₂ 4-isoxazolyl 1374 3-NH₂C₆H₄CH₂ 4-HOC₆H₄ 1375 3-NH₂C₆H₄CH₂ 3-HOC₆H₄ 1376 3-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1377 3-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1378 3-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1379 4-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 1380 4-NH₂C₆H₄CH₂ 3-MeOC₆H₄ 1381 4-NH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1382 4-NH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1383 4-NH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1384 4-NH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1385 4-NH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1386 4-NH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1387 4-NH₂C₆H₄CH₂ 4-pyridyl 1388 4-NH₂C₆H₄CH₂ 3-pyridyl 1389 4-NH₂C₆H₄CH₂ 2-pyridyl 1390 4-NH₂C₆H₄CH₂ 2-thiazolyl 1391 4-NH₂C₆H₄CH₂ 2-pyrazolyl 1392 4-NH₂C₆H₄CH₂ 5-isoquinolyl 1393 4-NH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1394 4-NH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1395 4-NH₂C₆H₄CH₂ 2-imidazolyl 1396 4-NH₂C₆H₄CH₂ 2-oxazolyl 1397 4-NH₂C₆H₄CH₂ 4-isoxazolyl 1398 4-NH₂C₆H₄CH₂ 4-HOC₆H₄ 1399 4-NH₂C₆H₄CH₂ 3-HOC₆H₄ 1400 4-NH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1401 4-NH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1402 4-NH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1403 2-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1404 2-MeOC₆H₄CH₂ 3-MeOC₆H₄ 1405 2-MeOC₆H₄CH₂ 4-NH₂C₆H₄ 1406 2-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 1407 2-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 1408 2-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 1409 2-MeOC₆H₄CH₂ 3-Me₂NC₆H₄ 1410 2-MeOC₆H₄CH₂ 2-Me₂NC₆H₄ 1411 2-MeOC₆H₄CH₂ 4-pyridyl 1412 2-MeOC₆H₄CH₂ 3-pyridyl 1413 2-MeOC₆H₄CH₂ 2-pyridyl 1414 2-MeOC₆H₄CH₂ 2-thiazolyl 1415 2-MeOC₆H₄CH₂ 2-pyrazolyl 1416 2-MeOC₆H₄CH₂ 5-isoquinolyl 1417 2-MeOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1418 2-MeOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1419 2-MeOC₆H₄CH₂ 2-imidazolyl 1420 2-MeOC₆H₄CH₂ 2-oxazolyl 1421 2-MeOC₆H₄CH₂ 4-isoxazolyl 1422 2-MeOC₆H₄CH₂ 4-HOC₆H₄ 1423 2-MeOC₆H₄CH₂ 3-HOC₆H₄ 1424 2-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 1425 2-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1426 2-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1427 3-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1428 3-MeOC₆H₄CH₂ 3-MeOC₆H₄ 1429 3-MeOC₆H₄CH₂ 4-NH₂C₆H₄ 1430 3-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 1431 3-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 1432 3-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 1433 3-MeOC₆H₄CH₂ 3-Me₂NC₆H₄ 1434 3-MeOC₆H₄CH₂ 2-Me₂NC₆H₄ 1435 3-MeOC₆H₄CH₂ 4-pyridyl 1436 3-MeOC₆H₄CH₂ 3-pyridyl 1437 3-MeOC₆H₄CH₂ 2-pyridyl 1438 3-MeOC₆H₄CH₂ 2-thiazolyl 1439 3-MeOC₆H₄CH₂ 2-pyrazolyl 1440 3-MeOC₆H₄CH₂ 5-isoquinolyl 1441 3-MeOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1442 3-MeOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1443 3-MeOC₆H₄CH₂ 2-imidazolyl 1444 3-MeOC₆H₄CH₂ 2-oxazolyl 1445 3-MeOC₆H₄CH₂ 4-isoxazolyl 1446 3-MeOC₆H₄CH₂ 4-HOC₆H₄ 1447 3-MeOC₆H₄CH₂ 3-HOC₆H₄ 1448 3-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 1449 3-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1450 3-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1451 4-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1452 4-MeOC₆H₄CH₂ 3-MeOC₆H₄ 1453 4-MeOC₆H₄CH₂ 4-NH₂C₆H₄ 1454 4-MeOC₆H₄CH₂ 3-NH₂C₆H₄ 1455 4-MeOC₆H₄CH₂ 2-NH₂C₆H₄ 1456 4-MeOC₆H₄CH₂ 4-Me₂NC₆H₄ 1457 4-MeOC₆H₄CH₂ 3-Me₂NC₆H₄ 1458 4-MeOC₆H₄CH₂ 2-Me₂NC₆H₄ 1459 4-MeOC₆H₄CH₂ 4-pyridyl 1460 4-MeOC₆H₄CH₂ 3-pyridyl 1461 4-MeOC₆H₄CH₂ 2-pyridyl 1462 4-MeOC₆H₄CH₂ 2-thiazolyl 1463 4-MeOC₆H₄CH₂ 2-pyrazolyl 1464 4-MeOC₆H₄CH₂ 5-isoquinolyl 1465 4-MeOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1466 4-MeOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1467 4-MeOC₆H₄CH₂ 2-imidazolyl 1468 4-MeOC₆H₄CH₂ 2-oxazolyl 1469 4-MeOC₆H₄CH₂ 4-isoxazolyl 1470 4-MeOC₆H₄CH₂ 4-HOC₆H₄ 1471 4-MeOC₆H₄CH₂ 3-HOC₆H₄ 1472 4-MeOC₆H₄CH₂ 3,4-diHOC₆H₄ 1473 4-MeOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1474 4-MeOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1475 2-HOC₆H₄CH₂ 4-MeOC₆H₄ 1476 2-HOC₆H₄CH₂ 3-MeOC₆H₄ 1477 2-HOC₆H₄CH₂ 4-NH₂C₆H₄ 1478 2-HOC₆H₄CH₂ 3-NH₂C₆H₄ 1479 2-HOC₆H₄CH₂ 2-NH₂C₆H₄ 1480 2-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 1481 2-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 1482 2-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 1483 2-HOC₆H₄CH₂ 4-pyridyl 1484 2-HOC₆H₄CH₂ 3-pyridyl 1485 2-HOC₆H₄CH₂ 2-pyridyl 1486 2-HOC₆H₄CH₂ 2-thiazolyl 1487 2-HOC₆H₄CH₂ 2-pyrazolyl 1488 2-HOC₆H₄CH₂ 5-isoquinolyl 1489 2-HOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1490 2-HOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1491 2-HOC₆H₄CH₂ 2-imidazolyl 1492 2-HOC₆H₄CH₂ 2-oxazolyl 1493 2-HOC₆H₄CH₂ 4-isoxazolyl 1494 2-HOC₆H₄CH₂ 4-HOC₆H₄ 1495 2-HOC₆H₄CH₂ 3-HOC₆H₄ 1496 2-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 1497 2-HOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1498 2-HOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1499 3-HOC₆H₄CH₂ 4-MeOC₆H₄ 1500 3-HOC₆H₄CH₂ 3-MeOC₆H₄ 1501 3-HOC₆H₄CH₂ 4-NH₂C₆H₄ 1502 3-HOC₆H₄CH₂ 3-NH₂C₆H₄ 1503 3-HOC₆H₄CH₂ 2-NH₂C₆H₄ 1504 3-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 1505 3-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 1506 3-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 1507 3-HOC₆H₄CH₂ 4-pyridyl 1508 3-HOC₆H₄CH₂ 3-pyridyl 1509 3-HOC₆H₄CH₂ 2-pyridyl 1510 3-HOC₆H₄CH₂ 2-thiazolyl 1511 3-HOC₆H₄CH₂ 2-pyrazolyl 1512 3-HOC₆H₄CH₂ 5-isoquinolyl 1513 3-HOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1514 3-HOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1514 3-HOC₆H₄CH₂ 2-imidazolyl 1516 3-HOC₆H₄CH₂ 2-oxazolyl 1517 3-HOC₆H₄CH₂ 4-isoxazolyl 1518 3-HOC₆H₄CH₂ 4-HOC₆H₄ 1519 3-HOC₆H₄CH₂ 3-HOC₆H₄ 1520 3-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 1521 3-HOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1522 3-HOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1523 4-HOC₆H₄CH₂ 4-MeOC₆H₄ 1524 4-HOC₆H₄CH₂ 3-MeOC₆H₄ 1525 4-HOC₆H₄CH₂ 4-NH₂C₆H₄ 1526 4-HOC₆H₄CH₂ 3-NH₂C₆H₄ 1527 4-HOC₆H₄CH₂ 2-NH₂C₆H₄ 1528 4-HOC₆H₄CH₂ 4-Me₂NC₆H₄ 1529 4-HOC₆H₄CH₂ 3-Me₂NC₆H₄ 1530 4-HOC₆H₄CH₂ 2-Me₂NC₆H₄ 1531 4-HOC₆H₄CH₂ 4-pyridyl 1532 4-HOC₆H₄CH₂ 3-pyridyl 1533 4-HOC₆H₄CH₂ 2-pyridyl 1534 4-HOC₆H₄CH₂ 2-thiazolyl 1535 4-HOC₆H₄CH₂ 2-pyrazolyl 1536 4-HOC₆H₄CH₂ 5-isoquinolyl 1537 4-HOC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1538 4-HOC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1539 4-HOC₆H₄CH₂ 2-imidazolyl 1540 4-HOC₆H₄CH₂ 2-oxazolyl 1541 4-HOC₆H₄CH₂ 4-isoxazolyl 1542 4-HOC₆H₄CH₂ 4-HOC₆H₄ 1543 4-HOC₆H₄CH₂ 3-HOC₆H₄ 1544 4-HOC₆H₄CH₂ 3,4-diHOC₆H₄ 1545 4-HOC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1546 4-HOC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1547 4-ClC₆H₄CH₂ 4-MeOC₆H₄ 1548 4-ClC₆H₄CH₂ 3-MeOC₆H₄ 1549 4-ClC₆H₄CH₂ 4-NH₂C₆H₄ 1550 4-ClC₆H₄CH₂ 3-NH₂C₆H₄ 1551 4-ClC₆H₄CH₂ 2-NH₂C₆H₄ 1552 4-ClC₆H₄CH₂ 4-Me₂NC₆H₄ 1553 4-ClC₆H₄CH₂ 3-Me₂NC₆H₄ 1554 4-ClC₆H₄CH₂ 2-Me₂NC₆H₄ 1555 4-ClC₆H₄CH₂ 4-pyridyl 1556 4-ClC₆H₄CH₂ 3-pyridyl 1557 4-ClC₆H₄CH₂ 2-pyridyl 1558 4-ClC₆H₄CH₂ 2-thiazolyl 1559 4-ClC₆H₄CH₂ 2-pyrazolyl 1560 4-ClC₆H₄CH₂ 5-isoquinolyl 1561 4-ClC₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1562 4-ClC₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1563 4-ClC₆H₄CH₂ 2-imidazolyl 1564 4-ClC₆H₄CH₂ 2-oxazolyl 1565 4-ClC₆H₄CH₂ 4-isoxazolyl 1566 4-ClC₆H₄CH₂ 4-HOC₆H₄ 1567 4-ClC₆H₄CH₂ 3-HOC₆H₄ 1568 4-ClC₆H₄CH₂ 3,4-diHOC₆H₄ 1569 4-ClC₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1570 4-ClC₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1571 2-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 1572 2-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 1573 2-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1574 2-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1575 2-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1576 2-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1577 2-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1578 2-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1579 2-NH₂CH₂C₆H₄CH₂ 4-pyridyl 1580 2-NH₂CH₂C₆H₄CH₂ 3-pyridyl 1581 2-NH₂CH₂C₆H₄CH₂ 2-pyridyl 1582 2-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 1583 2-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 1584 2-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 1585 2-NH₂CH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1586 2-NH₂CH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1587 2-NH₂CH₂C₆H₄CH₂ 2-imidazolyl 1588 2-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 1589 2-NH₂CH₂C₆H₄CH₂ 4-isoxazolyl 1590 2-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 1591 2-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄ 1592 2-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1593 2-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1594 2-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1595 3-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 1596 3-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 1597 3-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1598 3-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1599 3-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1600 3-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1601 3-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1602 3-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1603 3-NH₂CH₂C₆H₄CH₂ 4-pyridyl 1604 3-NH₂CH₂C₆H₄CH₂ 3-pyridyl 1605 3-NH₂CH₂C₆H₄CH₂ 2-pyridyl 1606 3-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 1607 3-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 1608 3-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 1609 3-NH₂CH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1610 3-NH₂CH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1611 3-NH₂CH₂C₆H₄CH₂ 2-imidazolyl 1612 3-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 1613 3-NH₂CH₂C₆H₄CH₂ 4-isoxazolyl 1614 3-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 1615 3-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄ 1616 3-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1617 3-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1618 3-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1619 4-NH₂CH₂C₆H₄CH₂ 4-MeOC₆H₄ 1620 4-NH₂CH₂C₆H₄CH₂ 3-MeOC₆H₄ 1621 4-NH₂CH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1622 4-NH₂CH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1623 4-NH₂CH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1624 4-NH₂CH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1625 4-NH₂CH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1626 4-NH₂CH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1627 4-NH₂CH₂C₆H₄CH₂ 4-pyridyl 1628 4-NH₂CH₂C₆H₄CH₂ 3-pyridyl 1629 4-NH₂CH₂C₆H₄CH₂ 2-pyridyl 1630 4-NH₂CH₂C₆H₄CH₂ 2-thiazolyl 1631 4-NH₂CH₂C₆H₄CH₂ 2-pyrazolyl 1632 4-NH₂CH₂C₆H₄CH₂ 5-isoquinolyl 1633 4-NH₂CH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1634 4-NH₂CH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1635 4-NH₂CH₂C₆H₄CH₂ 2-imidazolyl 1636 4-NH₂CH₂C₆H₄CH₂ 2-oxazolyl 1637 4-NH₂CH₂C₆H₄CH₂ 4-isoxazolyl 1638 4-NH₂CH₂C₆H₄CH₂ 4-HOC₆H₄ 1639 4-NH₂CH₂C₆H₄CH₂ 3-HOC₆H₄ 1640 4-NH₂CH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1641 4-NH₂CH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1642 4-NH₂CH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1643 2-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 1644 2-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 1645 2-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1646 2-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1647 2-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1648 2-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1649 2-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1650 2-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1651 2-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 1652 2-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 1653 2-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 1654 2-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 1655 2-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 1656 2-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 1657 2-Me₂NCH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1658 2-Me₂NCH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1659 2-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 1660 2-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 1661 2-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 1662 2-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 1663 2-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 1664 2-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1665 2-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1666 2-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1667 3-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 1668 3-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 1669 3-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1670 3-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1671 3-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1672 3-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1673 3-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1674 3-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1675 3-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 1676 3-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 1677 3-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 1678 3-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 1679 3-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 1680 3-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 1681 3-Me₂NCH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1682 3-Me₂NCH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1683 3-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 1684 3-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 1685 3-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 1686 3-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 1687 3-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 1688 3-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1689 3-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1690 3-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄ 1691 4-Me₂NCH₂C₆H₄CH₂ 4-MeOC₆H₄ 1692 4-Me₂NCH₂C₆H₄CH₂ 3-MeOC₆H₄ 1693 4-Me₂NCH₂C₆H₄CH₂ 4-NH₂C₆H₄ 1694 4-Me₂NCH₂C₆H₄CH₂ 3-NH₂C₆H₄ 1695 4-Me₂NCH₂C₆H₄CH₂ 2-NH₂C₆H₄ 1696 4-Me₂NCH₂C₆H₄CH₂ 4-Me₂NC₆H₄ 1697 4-Me₂NCH₂C₆H₄CH₂ 3-Me₂NC₆H₄ 1698 4-Me₂NCH₂C₆H₄CH₂ 2-Me₂NC₆H₄ 1699 4-Me₂NCH₂C₆H₄CH₂ 4-pyridyl 1700 4-Me₂NCH₂C₆H₄CH₂ 3-pyridyl 1701 4-Me₂NCH₂C₆H₄CH₂ 2-pyridyl 1702 4-Me₂NCH₂C₆H₄CH₂ 2-thiazolyl 1703 4-Me₂NCH₂C₆H₄CH₂ 2-pyrazolyl 1704 4-Me₂NCH₂C₆H₄CH₂ 5-isoquinolyl 1705 4-Me₂NCH₂C₆H₄CH₂ 3,4- methylenedioxyC₆H₃ 1706 4-Me₂NCH₂C₆H₄CH₂ 3,4- ethylenedioxyC₆H₃ 1707 4-Me₂NCH₂C₆H₄CH₂ 2-imidazolyl 1708 4-Me₂NCH₂C₆H₄CH₂ 2-oxazolyl 1709 4-Me₂NCH₂C₆H₄CH₂ 4-isoxazolyl 1710 4-Me₂NCH₂C₆H₄CH₂ 4-HOC₆H₄ 1711 4-Me₂NCH₂C₆H₄CH₂ 3-HOC₆H₄ 1712 4-Me₂NCH₂C₆H₄CH₂ 3,4-diHOC₆H₄ 1713 4-Me₂NCH₂C₆H₄CH₂ 4-NH₂CH₂C₆H₄ 1714 4-Me₂NCH₂C₆H₄CH₂ 3-NH₂CH₂C₆H₄

TABLE 4

Example Number R¹ R² 1715 Methyl 4-MeOC₆H₄ 1716 ClCH₂ 4-MeOC₆H₄ 1717 cyclopropyl 4-MeOC₆H₄ 1718 isopropyl 4-MeOC₆H₄ 1719 ethyl 4-MeOC₆H₄ 1720 cyclopentyl 4-MeOC₆H₄ 1721 cyclobutyl 4-MeOC₆H₄ 1722 benzyl 4-MeOC₆H₄ 1723 n-propyl 4-MeOC₆H₄ 1724 4-ClC₆H₄CH₂ 4-MeOC₆H₄ 1725 3-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1726 4-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1727 3,4-diMeOC₆H₄CH₂ 4-MeOC₆H₄ 1728 2,5-diMeOC₆H₄CH₂ 4-MeOC₆H₄ 1729 Methyl 2-MeOC₆H₄ 1730 Methyl 3,4-diMeOC₆H₄ 1731 3,4-(OCH₂O)C₆H₄CH₂ 4-MeOC₆H₄ 1732 3-thiophenylCH₂ 4-MeOC₆H₄ 1733 2-MeOC₆H₄CH₂ 4-MeOC₆H₄ 1734 3,4-diClOC₆H₄CH₂ 4-MeOC₆H₄ 1735 2,4-diClOC₆H₄CH₂ 4-MeOC₆H₄ 1736 2-ClC₆H₄CH₂ 4-MeOC₆H₄ 1737 H₂NCH₂ 4-MeOC₆H₄ 1738 HOCH₂NHCH₂CH₂ 4-MeOC₆H₄ 1739 Me₂NCH₂ 4-MeOC₆H₄ 1740 piperazinylCH₂ 4-MeOC₆H₄ 1741 4-Me-piperazinylCH₂ 4-MeOC₆H₄ 1742 4-HOCH₂CH₂- 4-MeOC₆H₄ piperazinylCH₂ 1743 piperidinylCH₂ 4-MeOC₆H₄ 1744 4-NH₂CH₂- 4-MeOC₆H₄ piperidinylCH₂ 1745 CH₃CH₂NHCH₂ 4-MeOC₆H₄ 1746 thiomorpholinylCH₂ 4-MeOC₆H₄ 1747 morpholinylCH₂ 4-MeOC₆H₄ 1748 pyyrolidinylCH₂ 4-MeOC₆H₄ 1749 4-pyridylCH₂NHCH₂ 4-MeOC₆H₄ 1750 4-CH₃CONHC₆H₄CH₂ 4-MeOC₆H₄ 1751 4-CH₃OCONHC₆H₄CH₂ 4-MeOC₆H₄ 1752 4-NH₂CH₂CONHC₆H₄CH₂ 4-MeOC₆H₄ 1753 4-Me₂NCH₂CONHC₆H₄CH₂ 4-MeCC₆H₄ 1754 4-N₃C₆H₄CH₂ 4-MeOC₆H₄ 1755 4-NH₂C₆H₄CH₂ 4-MeOC₆H₄ 1156 C₆H₅NH 4-MeOC₆H₄ 1757 CH₃CH₂CH₂NH 4-MeOC₆H₄ 1758 4-NH₂C₆H₄CH₂NH 4-MeOC₆H₄ 1759 4-pyridyCH₂NH 4-MeOC₆H₄ 1760 Methyl 4-HOC₆H₄ 1761 H 4-MeOC₆H₄ 1762 Methyl 3-pyridyl 1763 Methyl 4-pyridyl 1764 H 4-pyridyl 1765 Methyl C₆H₅ 1766 Methyl 4-MeSC₆H₄ 1767 Methyl 4-MeSO₂C₆H₄ 1768 Methyl 4-Me₂NC₆H₄ 1769 morpholinylCH₂ 4-Me₂NC₆H₄ 1770 Me₂NCH₂ 4-Me₂NC₆H₄ 1771 Me₂NCH₂ 4-(piperdinyl)C₆H₄ 1772 Me₂NCH₂ 4- (morpholinyl)C₆H₄ 1773 Me₂NCH₂ 4-CH₃CH₂OC₆H₄ 1774 Me₂NCH₂ 4-CH₃CH₂CH₂CH₂C₆H₄ 1775 Me₂NCH₂ 4-CH₃CH₂C₆H₄ 1776 Me₂NCH₂ 4-CH₃CH₂CH₂C₆H₄ 

What is claimed is:
 1. A method of inhibiting the division of a cell which comprises contacting the cell with a composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of the formula (I):

or a stereoisomer or pharmaceutically acceptable salt form thereof, wherein: X is selected from the group: O, S, and NR; R is selected from the group: H, C₁₋₄ alkyl, and NR⁵R^(5a); R¹ is selected from the group: H, C₁₋₁₀ alkyl substituted with 0-3 R^(C), C₂₋₁₀ alkenyl substituted with 0-3 R^(c), C₂₋₁₀ alkynyl substituted with 0-3 R^(c), —NHR⁴, C₃₋₁₀ carbocycle substtuted with 0-5 R^(a), and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R^(b); R^(a) is independently at each occurrence selected from the group: halo, —CN, N₃, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), ═O, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, SO₂NR³R^(3a), SO₂R^(3b), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S; alternatively, when two R^(a)'s are present on adjacent carbon atoms they combine to form —OCH₂O— or —OCH₂CH₂O—; R^(b) is independently at each occurrence selected from the group: halo, —CN, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), and SO₂R^(3b); R^(c) is independently at each occurrence selected from the group: halo, —CN, NO₂, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR⁵NR⁵R^(5a), NR³C(O)OR³, NR³C(O)R³,═O, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂N³R^(3a), SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R³; R² is selected from the group: H, C₁₋₁₀ alkyl substituted with 0-3 R^(c), C₂₋₁₀ alkenyl substituted with 0-3 R^(c), C₂₋₁₀ alkynyl substituted with 0-3 R^(c), —(CF₂)_(m)CF₃, C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 3-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S and substituted with 0-5 R^(b); R³ is selected from the group: H, halo, —CN, N₃, NO₂, C₁₋₄ haloalkyl, NR⁵R^(5a), NR⁵NR⁵R^(5a), NR⁵C(O)OR⁵, NR⁵C(O)R⁵,═O, OR⁵, COR⁵, CO₂R⁵, CONR⁵R^(5a), NHC(O)NR⁵R^(5a), NHC(S)NR⁵R^(5a), SO₂NR⁵R^(5a), SO₂R^(5b), C₁ alkyl, phenyl, and benzyl; R^(3a) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl; alternatively, R³ and R^(3a), together with the nitrogen atom to which they are attached, form a heterocycle having 4-8 atoms in the ring and containing an additional 0-1 N, S, or O atom; R^(3b) is selected from the group: H, C₁₋₄ alkyl, phenyl, and benzyl; R⁴ is independently at each occurrence selected from the group: H, —CN, C₁₋₄ alkyl, C₁₋₄ haloalkyl, NR³R^(3a), NR³C(O)OR³, NR³C(O)R³, OR³, COR³, CO₂R³, CONR³R^(3a), NHC(O)NR³R^(3a), NHC(S)NR³R^(3a), SO₂NR³R^(3a), SO₂R^(3b), C₃₋₁₀ carbocycle substituted with 0-5 R^(a), and 5-10 membered heterocycle containing from 1-4 heteroatoms selected from O, N, and S, substituted with 0-3 R³; R⁵ is independently selected from the group: H, C₁₋₄ alkyl, phenyl and benzyl; R^(5a) is independently selected from the group: H, C₁₋₄ alkyl, phenyl and benzyl; R^(5b) is independently selected from the group: H, C₁₋₄ alkyl, phenyl and benzyl; and m is selected from 0, 1, 2, and 3., provided that R² my not be an unsubstituted branched alkyl group when R¹ is CH₃. 